Sample records for sensorineuralem hoerverlust vor

Several methods for deriving position from VOR (without DME) have been developed and evaluated in this study. These methods permit navigation to arbitrary waypoints using either two VOR's or one VOR and a clock. These algorithms have been tested in computer simulations and in flight tests. The single VOR method appears to be the most practical and is a candidate for an automated light plane area navigation system, called VORNAV.

.../DME facility which currently serves as an end point for the route. DATES: Comments must be received on... Portland, OR VOR/ DME, which serves as the northern endpoint of the route, is scheduled to be... Portland VOR/DME. VOR Federal airways are published in paragraph 6010, of FAA Order 7400.9W dated August...

The experimental concept and findings from a recent manned orbital spaceflight are described. Together with ongoing terrestrial and parabolic studies, the present experiment is intended to further our knowledge of the sensory integrative processing of information from the semicircular canals and the otolithic receptors, and to quantify the presumed otolithic adaptation to altered gravito-inertial force environments in a more reliable manner than to date. The experiment included measurement of the basic vestibulo-oculomotor response during active head rotation about each of the three orthogonal axes. Priority was given to the recording of ocular torsion, as elicited by head oscillation about the roll axis, and thus due to the concomitant stimulation of the semicircular canals and otolith receptors. Videooculography was employed for the measurement of eye movements; head movement was measured by three orthogonally arranged angular rate sensors and a triaxial linear accelerometer device. All signals were recorded synchronously on a video/data recorder. Preliminary results indicate alterations in the torsional VOR under zero-g conditions, suggesting an adaptive modification of the torsional VOR gain over the course of the 6-day orbital flight. In addition, the inflight test findings yielded discrepancies between intended and performed head movement, indicating impairment in sensorimotor coordination under prolonged microgravity conditions.

The vestibulo-ocular reflex (VOR) is normally characterized by the gain and phase of slow-phase velocity (SPV) relative to the stimulus velocity. Although this is perfectly satisfactory for steady-state sinusoidal oscillations about a single axis, it is less useful when applied to transient responses. The well-known decay of nystagmus following a step change of head velocity approximately follows a double exponential, with an initial amplitude (A), a long time constant (tau), and an adaptation time constant (tau(a)). We have developed a means of representing the transient response for a complex head velocity stimulus as experienced during high-speed artificial gravity (AG) experiments. When a subject, lying supine on a rotating horizontal platform, makes a yaw head movement of amplitude theta, the vertical semicircular canals experience a step in angular velocity. The pitch stimulus is equal to the change in the component of the centrifuge angular velocity (omega(c)) aligned with the interaural axis, and gives rise to a vertical VOR. The magnitude of the step change is omega(c) sin theta. The SPV is approximated by an exponential decay of amplitude A and single time constant tau, and then normalized relative to this stimulus step. MATLAB scripts filter the raw eye position data to remove noise, blinks, and saccades, differentiate the signal, and remove fast phases to obtain SPV. The amplitude of the fitted SPV exponential is divided by omega(c) sin theta to obtain the normalized SPV. A and tau are shown to behave differently as subjects adapt to repeated head movements of different amplitudes.

... to the scheduled decommissioning of the Moultrie, GA, VOR/DME facility which forms a point along the..., GA, VOR/DME, which forms a point along the route, is scheduled to be decommissioned, thus the route... would redefine the position of the Moultrie, GA, VOR/DME with a navigation fix formed by...

Demonstration that updating an inertial navigation system (INS) with VOR/DME information (from one or two stations) by means of a maximum-likelihood filter results in substantial improvements in navigational accuracy over that obtained by the use of a single VOR/DME (current practice). When continuously updating, the use of a high-quality INS (0.01 deg/hr gyro drift) instead of a low-quality INS (1.0 deg/hr gyro drift) does not substantially improve position accuracy. In-flight alignment (or realignment) of an INS to an accuracy comparable to that of ground alignment can be accomplished by using two DMEs. Several reduced-order suboptimal filters were found to perform nearly optimally.

... Federal Aviation Administration 14 CFR Part 71 RIN 2120-AA66 Modification of VOR Federal Airway V-537, GA..., GA, VOR/DME navigation aid which currently forms a point along the route. DATES: Effective date 0901... radial from the Macon, GA, VORTAC that had been planned to form an intersection along the route...

Vestibulo-ocular reflexes (VORs) stabilize the eyes during head motion. During Earth-horizontal (E-H) pitch or roll rotations, canal and otolith stimuli occur together. In Earth-vertical (E-V) pitch or roll rotations, only canal signals occur. In cats and squirrel monkeys, pitch/roll VOR gains during E-H motion have been shown to be larger than during E-V motion, implying that otolith modulation plays a role in producing angular VORs (aVORs). The present experiments replicated this experiment in rhesus monkeys, and examined how spaceflight affected AVOR gain. During yaw, pitch and roll (0.5 - 1.0 Hz, 40-50 deg/s pk) motion, 3-d eye movements were recorded in four Rhesus monkeys using scleral search coils. Mean E-H and E-V pitch VOR gains were 0.85 and 0.71. Torsional VOR gains during E-H and E-V were 0.47 and 0.39. Gains are more compensatory during E-H pitch or roll. Two of the four monkeys flew for 11 days on the COSMOS 2229 Biosatellite. E-H pitch VOR gains were attenuated immediately (72 hrs) post-flight, with similar values to pre-flight E-V pitch gains. Horizontal yaw VOR gains were similar pre- and post-flight.

... Federal Aviation Administration 14 CFR Part 71 Modification of VOR Federal Airway V-14; Missouri AGENCY... amends VOR Federal airway V-14 in the vicinity of St. Louis, MO. The FAA is taking this action to correct the V-14 description contained in Part 71 to ensure it matches the information contained in the...

The vestibulo-ocular reflex (VOR) is essential in our daily life to stabilize retinal images during head movements. Balanced vestibular functionality secures optimal reflex performance which otherwise can be distorted by peripheral vestibular lesions. Luckily, vestibular compensation in different neuronal sites restores VOR function to some extent over time. Studying vestibular compensation gives insight into the possible mechanisms for plasticity in the brain. In this work, novel experimental analysis tools are employed to reevaluate the VOR characteristics following unilateral vestibular lesions and compensation. Our results suggest that following vestibular lesions, asymmetric performance of the VOR is not only limited to its gain. Vestibular compensation also causes asymmetric dynamics, i.e., different time constants for the VOR during leftward or rightward passive head rotation. Potential mechanisms for these experimental observations are provided using simulation studies. PMID:27065839

A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

... Measuring Equipment (VOR/ DME) navigation aid, which forms the northern most point of the airway, has been... service by the Ashland, WI, VOR/DME. DATES: Comments must be received on or before May 10, 2013. ADDRESSES... necessary because the Ashland, WI, VOR/DME, which serves as the northern endpoint of the airway, has...

Although one particular model of the cerebellum, as proposed by Marr and Albus, provides a formal framework for understanding how heterosynaptic plasticity of Purkinje cells might be used for motor learning, the physiological details remain largely an engima. Developments in computational neuroscience and artificial neural networks applied to real control problems are essential to understand fully how workspace errors associated with movement performances can be converted into motor-command errors, and how these errors can then be used as one kind of synaptic input by motor-learning algorithms that are based on biologically plausible rules involving heterosynaptic plasticity. These developments, as well as recent advances in the study of cellular mechanisms of synaptic plasticity, form the basis for the detailed computational models of cerebellar motor learning that have been proposed. These models provide hints toward resolving a long-standing controversy in the oculomotor literature regarding the sites of adaptive changes in the vestibuloocular reflex (VOR) and the optokinetic eye movement response (OKR), and suggest new experiments to elucidate general mechanisms of sensory motor learning.

... supplement the existing routes structure for aircraft navigating in an area of marginal radar coverage. This... aircraft navigating in an area of marginal radar coverage. VOR Federal airways are published in...

... of marginal radar coverage. This would enhance the efficiency of the National Airspace System (NAS... navigating in an area of marginal radar coverage. VOR Federal airways are published in paragraph 6010 of...

Little is known about the dependence of the roll angular vestibuloocular reflex (aVOR) on gravity or its gravity-dependent adaptive properties. To study gravity-dependent characteristics of the roll aVOR, monkeys were oscillated about a naso-occipital axis in darkness while upright or tilted. Roll aVOR gains were largest in the upright position and decreased by 7-15% as animals were tilted from the upright. Thus the unadapted roll aVOR gain has substantial gravitational dependence. Roll gains were also decreased or increased by 0.25 Hz, in- or out-of-phase rotation of the head and the visual surround while animals were prone, supine, upright, or in side-down positions. Gain changes, determined as a function of head tilt, were fit with a sinusoid; the amplitudes represented the amount of the gravity-dependent gain change, and the bias, the gravity-independent gain change. Gravity-dependent gain changes were absent or substantially smaller in roll (approximately 5%) than in yaw (25%) or pitch (17%), whereas gravity-independent gain changes were similar for roll, pitch, and yaw (approximately 20%). Thus the high-frequency roll aVOR gain has an inherent dependence on head orientation re gravity in the unadapted state, which is different from the yaw/pitch aVORs. This inherent gravitational dependence may explain why the adaptive circuits are not active when the head is tilted re gravity during roll aVOR adaptation. These behavioral differences support the idea that there is a fundamental difference in the central organization of canal-otolith convergence of the roll and yaw/pitch aVORs.

...; Hawaii AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action amends two VHF Omnidirectional Range (VOR) Federal airway legal descriptions in the State of Hawaii. The... Federal Airways, V-2 and V-21, located in the State of Hawaii by removing all references to...

The report presents a definition of a VOR/DME, airborne and ground systems simulation model. This description was drafted in response to a need in the creation of an advanced concepts simulation in which flight station design for the 1980 era can be postulated and examined. The simulation model described herein provides a reasonable representation of VOR/DME station in the continental United States including area coverage by type and noise errors. The detail in which the model has been cast provides the interested researcher with a moderate fidelity level simulator tool for conducting research and evaluation of navigator algorithms. Assumptions made within the development are listed and place certain responsibilities (data bases, communication with other simulation modules, uniform round earth, etc.) upon the researcher.

filtering and time-dependency,” Ergonomics , 613-626. Paddan, G. and M. Griffin (1988). “The transmission of translational seat vibration to the head...understand and describe the VOR in the presence of head slued imagery as a function of whole body low-frequency vibration. An experimental HMD was designed ...circuitry design to assisting with software coding. Finally, I would like to thank my beautiful fiancée for her love and support throughout the

The vestibulo-ocular reflex (VOR) mechanism triggers eye movements as a result of head motion in order to keep gaze stationary relative to the world. However, in order to shift the direction of the gaze along with head motion, the VOR mechanism must be overridden ("cancelled"). Two mechanisms have been proposed to explain this cancellation: a reduction of the VOR gain or activation of smooth pursuit (SP) eye movements in the opposite direction. We studied VOR cancellation using the magnetic search coil in six spinocerebellar ataxia type 3 (SCA-3) and four episodic ataxia type 2 (EA-2) patients, conditions that are known to have degraded SP but different degrees of VOR impairment. Abnormal VOR was found in two of the four EA-2 patients and all of the SCA-3 patients. All subjects possessed residual VOR, although when tested using head thrusts it was almost negligible in the SCA-3 patients. The EA-2 patients showed essentially no SP and the SCA-3 patients had poor SP. However, for all patients, the gain during VOR cancellation was comparable to normals. These results provide additional evidence that SP cancellation of the VOR cannot be the sole mechanism utilized in overriding the VOR in these patients.

In 1G, the apparent time constant (Td) of postrotatory SPV decay with the head tilted face down is 55% of that with head erect (Te). This phenomenon is called "nystagmus dumping" and has been attributed to G effects on VOR velocity storage. Similarly, postrotatory sensation duration with head tilted (Dd) is 32% of that when head erect (De). In parabolic flight, Te and De are 70% of 1-G values, but a pitch back dumping movement produces no further change. Te, Td, and Dd have not previously been measured in orbital flight. VOR and sensation duration was tested in 4 crewmembers in 4 preflight, 1 inflight (days 4 or 5) and 4 post flight sessions. Bitemporal EOG was recorded with eyes open in darkness. Instructions were to "gaze straight ahead," and indicate when "rotation sensation disappears or becomes ambiguous". Subjects were rotated CW and CCW head erect for 1 min at 120 degrees/s, stopped, and EOG was recorded for another 1 min. This procedure was then used to study dumping, except that immediately after chair stop, subjects pitched their head forward 90 degrees. SPV was calculated using order statistic filtering, and dropouts removed using an iterative model fitting method. Te and Td were determined by logarithmic linear regression of mean SPV for each subject. In orbit, 90 degrees pitch movement produced rapid subjective dumping, but not nystagmus dumping. Dd was noticeably shorter ("almost instantaneous") compared to preflight Dd. Te and Td in orbit were similar to preflight Te for 3/4 subjects (rather than to preflight Td as expected). No consistent VOR gain changes were seen in orbit. Although Te is known to decrease acutely in parabolic flight, a longer time constant was measured in 3/4 subjects after 4-5 days adaptation to weightlessness, suggesting a return of angular velocity storage.

In 1G, the apparent time constant (Td) of postrotatory SPV decay with the head tilted face down is 55% of that with head erect (Te). This phenomenon is called "nystagmus dumping" and has been attributed to G effects on VOR velocity storage. Similarly, postrotatory sensation duration with head tilted (Dd) is 32% of that when head erect (De). In parabolic flight, Te and De are 70% of 1-G values, but a pitch back dumping movement produces no further change. Te, Td, and Dd have not previously been measured in orbital flight. VOR and sensation duration was tested in 4 crewmembers in 4 preflight, 1 inflight (days 4 or 5) and 4 post flight sessions. Bitemporal EOG was recorded with eyes open in darkness. Instructions were to "gaze straight ahead," and indicate when "rotation sensation disappears or becomes ambiguous". Subjects were rotated CW and CCW head erect for 1 min at 120 degrees/s, stopped, and EOG was recorded for another 1 min. This procedure was then used to study dumping, except that immediately after chair stop, subjects pitched their head forward 90 degrees. SPV was calculated using order statistic filtering, and dropouts removed using an iterative model fitting method. Te and Td were determined by logarithmic linear regression of mean SPV for each subject. In orbit, 90 degrees pitch movement produced rapid subjective dumping, but not nystagmus dumping. Dd was noticeably shorter ("almost instantaneous") compared to preflight Dd. Te and Td in orbit were similar to preflight Te for 3/4 subjects (rather than to preflight Td as expected). No consistent VOR gain changes were seen in orbit. Although Te is known to decrease acutely in parabolic flight, a longer time constant was measured in 3/4 subjects after 4-5 days adaptation to weightlessness, suggesting a return of angular velocity storage.

High-velocity rotational stimuli have the potential to improve the diagnostic capabilities of clinical rotation testing by revealing nonlinear vestibulo-ocular reflex (VOR) responses that are indicative of asymmetric vestibular function. However, eye movements evoked by high-velocity rotations often are inconsistent over time and therefore do not yield reliable diagnostic measures. This study investigated whether use of a novel “visual guide” could improve the consistency and quality of VORs obtained during testing with pulse-step-sine (PSS) stimuli providing periodic high-velocity, horizontal-plane rotations with peak velocities up to 290 deg/s. The visual guide (narrow phosphorescent line spanning 180° field of view) was mounted horizontally on the rotation chair at the subject's eye level. Eight healthy human subjects were tested either in complete darkness while performing an alerting task, or while viewing the visual guide in an otherwise dark room. We found that the visual guide improved the quality of VOR responses as shown by an increased proportion of slow-phase velocity data segments retained for analysis, by a decreased variance of the processed eye velocity data, and by a reduction of outlying VOR response measures. We also found that the visual guide did not induce visual suppression because VOR gain measures were not diminished. PMID:18776595

We studied short-term (30 min) adaptation of the vestibulo-ocular reflex (VOR) in five normal humans using a "position error" stimulus without retinal image motion. Both before and after adaptation a velocity gain (peak slow-phase eye velocity/peak head velocity) and a position gain (total eye movement during chair rotation/amplitude of chair motion) were measured in darkness using search coils. The vestibular stimulus was a brief ( approximately 700 ms), 15 degrees chair rotation in darkness (peak velocity 43 degrees /s). To elicit adaptation, a straight-ahead fixation target disappeared during chair movement and when the chair stopped the target reappeared at a new location in front of the subject for gain-decrease (x0) adaptation, or 10 degrees opposite to chair motion for gain-increase (x1.67) adaptation. This position-error stimulus was effective at inducing VOR adaptation, though for gain-increase adaptation the primary strategy was to substitute augmenting saccades during rotation while for gain-decrease adaptation both corrective saccades and a decrease in slow-phase velocity occurred. Finally, the presence of the position-error signal alone, at the end of head rotation, without any attempt to fix upon it, was not sufficient to induce adaptation. Adaptation did occur, however, if the subject did make a saccade to the target after head rotation, or even if the subject paid attention to the new location of the target without actually looking at it.

The vestibulo-ocular reflex (VOR) is a well-known dual mode bifurcating system that consists of slow and fast modes associated with nystagmus and saccade, respectively. Estimation of continuous-time parameters of nystagmus and saccade models are known to be sensitive to estimation methodology, noise and sampling rate. The stable and accurate estimation of these parameters are critical for accurate disease modelling, clinical diagnosis, robotic control strategies, mission planning for space exploration and pilot safety, etc. This paper presents a novel indirect system identification method for the estimation of continuous-time parameters of VOR employing standardised least-squares with dual sampling rates in a sparse structure. This approach permits the stable and simultaneous estimation of both nystagmus and saccade data. The efficacy of this approach is demonstrated via simulation of a continuous-time model of VOR with typical parameters found in clinical studies and in the presence of output additive noise.

The gain of the vertical angular vestibulo-ocular reflex (aVOR) was adaptively increased and decreased in a side-down head orientation for 4 h in two cynomolgus monkeys. Adaptation was performed at 0.25, 1, 2, or 4 Hz. The gravity-dependent and -independent gain changes were determined over a range of head orientations from left-side-down to right-side-down at frequencies from 0.25 to 10 Hz, before and after adaptation. Gain changes vs. frequency data were fit with a Gaussian to determine the frequency at which the peak gain change occurred, as well as the tuning width. The frequency at which the peak gravity-dependent gain change occurred was approximately equal to the frequency of adaptation, and the width increased monotonically with increases in the frequency of adaptation. The gravity-independent component was tuned to the adaptive frequency of 0.25 Hz but was uniformly distributed over all frequencies when the adaptation frequency was 1-4 Hz. The amplitude of the gravity-independent gain changes was larger after the aVOR gain decrease than after the gain increase across all tested frequencies. For the aVOR gain decrease, the phase lagged about 4° for frequencies below the adaptation frequency and led for frequencies above the adaptation frequency. For gain increases, the phase relationship as a function of frequency was inverted. This study demonstrates that the previously described dependence of aVOR gain adaptation on frequency is a property of the gravity-dependent component of the aVOR only. The gravity-independent component of the aVOR had a substantial tuning curve only at an adaptation frequency of 0.25 Hz.

... because the Chadron VOR distance measuring equipment (DME), included as part of the V-81, V-89, and V-169 route structure, is being renamed the Toadstool VOR/DME to avoid confusion with Chadron Airport that.../DME and the Chadron Airport share the same name and identifier (CDR), but are located...

... across the United States-Mexican border. DATES: Comments must be received on or before February 6, 2012... Imperial, CA VORTAC. These amendments would benefit cross-border navigation. Additionally, fixes would be established at the border crossing points to simplify air traffic control coordination of flights. VOR...

Electromagnetic coupling measurements were performed from numerous passenger cabin locations to aircraft instrument landing system localizer (LOC) and VHF Omni-Ranging (VOR) systems. This paper presents and compares the data for B-757 and B-737 airplanes, and provides a basis for fuzzy modeling of coupling patterns in different types of airplanes and airplanes with different antenna locations.

To compare and contrast the neural mechanisms that contribute to vestibular perception and action, we measured vestibuloocular reflexes (VOR) and perceptions of tilt and translation. We took advantage of the well-known ambiguity that the otolith organs respond to both linear acceleration and tilt with respect to gravity and investigated the mechanisms by which this ambiguity is resolved. A new motion paradigm that combined roll tilt with inter-aural translation ("Tilt&Translation") was used; subjects were sinusoidally (0.8 Hz) roll tilted but with their ears above or below the rotation axis. This paradigm provided sinusoidal roll canal cues that were the same across trials while providing otolith cues that varied linearly with ear position relative to the earth-horizontal rotation axis. We found that perceived tilt and translation depended on canal cues, with substantial roll tilt and inter-aural translation perceptions reported even when the otolith organs measured no inter-aural force. These findings match internal model predictions that rotational cues from the canals influence the neural processing of otolith cues. We also found horizontal translational VORs that varied linearly with radius; a minimal response was measured when the otolith organs transduced little or no inter-aural force. Hence, the horizontal translational VOR was dependent on otolith cues but independent of canal cues. These findings match predictions that translational VORs are elicited by simple filtering of otolith signals. We conclude that internal models govern human perception of tilt and translation at 0.8 Hz and that high-pass filtering governs the human translational VOR at this same frequency.

Control of locomotion requires precise interaction between several sensorimotor subsystems. During locomotion the performer must satisfy two performance criteria: maintain stable forward translation and to stabilize gaze (McDonald, et al., 1997). Precise coordination demands integration of multiple sensorimotor subsystems for fulfilling both criteria. In order to test the general hypothesis that the whole body can serve as an integrated gaze stabilization system, we have previously investigated how the multiple, interdependent full-body sensorimotor subsystems respond to changes in gaze stabilization task constraints during locomotion (Mulavara and Bloomberg, 2003). The results suggest that the full body contributes to gaze stabilization during locomotion, and that its different functional elements respond to changes in visual task constraints. The goal of this study was to determine how the multiple, interdependent, full-body sensorimotor subsystems aiding gaze stabilization during locomotion are functionally coordinated after the vestibulo-ocular reflex (VOR) gain has been altered. We investigated the potential of adaptive remodeling of the full-body gaze control system following exposure to visual-vestibular conflict known to adaptively reduce the VOR. Subjects (n=14) walked (6.4 km/h) on the treadmill before and after they were exposed to 0.5X manifying lenses worn for 30 minutes during self-generated sinusoidal vertical head rotations performed while seated. In this study we measured: temporal parameters of gait, full body sagittal plane segmental kinematics of the head, trunk, thigh, shank and foot, accelerations along the vertical axis at the head and the shank, and the vertical forces acting on the support surface. Results indicate that, following exposure to the 0.5X minifying lenses, there was a significant increase in the duration of stance and stride times, alteration in the amplitude of head movement with respect to space and a significant increase in

A "Multimode" or "switched" system is one that switches between various modes of operation. When a switch occurs from one mode to another, a discontinuity may result followed by a smooth evolution under the new regime. Characterizing the switching behavior of these systems is not well understood and, therefore, identification of multimode systems typically requires a preprocessing step to classify the observed data according to a mode of operation. A further consequence of the switched nature of these systems is that data available for parameter estimation of any subsystem may be inadequate. As such, identification and parameter estimation of multimode systems remains an unresolved problem. In this paper, we 1) show that the NARMAX model structure can be used to describe the impulsive-smooth behavior of switched systems, 2) propose a modified extended least squares (MELS) algorithm to estimate the coefficients of such models, and 3) demonstrate its applicability to simulated and real data from the Vestibulo-Ocular Reflex (VOR). The approach will also allow the identification of other nonlinear bio-systems, suspected of containing "hard" nonlinearities.

It is shown that although RNAV is particularly valuable for the personal transportation segment of general aviation, it has not gained complete acceptance. This is due, in part, to its high cost and the necessary special-handling air traffic control. VOR/DME RNAV calculations are ideally suited for analog computers, and the use of microprocessor technology has been suggested for reducing RNAV costs. Three navigation systems, VOR, Omega, and DR, are compared for common navigational difficulties, such as station geometry, siting errors, ground disturbances, and terminal area coverage. The Kalman filtering technique is described with reference to the disadvantages when using a system including standard microprocessors. An integrated navigation system, using input data from various low-cost sensor systems, is presented and current simulation studies are noted.

To investigate the neural mechanisms that humans use to process the ambiguous force measured by the otolith organs, we measured vestibuloocular reflexes (VORs) and perceptions of tilt and translation. One primary goal was to determine if the same, or different, mechanisms contribute to vestibular perception and action. We used motion paradigms that provided identical sinusoidal inter-aural otolith cues across a broad frequency range. We accomplished this by sinusoidally tilting (20 degrees, 0.005-0.7 Hz) subjects in roll about an earth-horizontal, head-centered, rotation axis ("Tilt") or sinusoidally accelerating (3.3 m/s2, 0.005-0.7 Hz) subjects along their inter-aural axis ("Translation"). While identical inter-aural otolith cues were provided by these motion paradigms, the canal cues were substantially different because roll rotations were present during Tilt but not during Translation. We found that perception was dependent on canal cues because the reported perceptions of both roll tilt and inter-aural translation were substantially different during Translation and Tilt. These findings match internal model predictions that rotational cues from the canals influence the neural processing of otolith cues. We also found horizontal translational VORs at frequencies >0.2 Hz during both Translation and Tilt. These responses were dependent on otolith cues and match simple filtering predictions that translational VORs include contributions via simple high-pass filtering of otolith cues. More generally, these findings demonstrate that internal models govern human vestibular "perception" across a broad range of frequencies and that simple high-pass filters contribute to human horizontal translational VORs ("action") at frequencies above approximately 0.2 Hz.

1. The adaptive plasticity of the vestibuloocular reflex (VOR) following a selective lesion of the peripheral vestibular organs was investigated in rhesus monkeys whose lateral semicircular canals were inactivated by plugging of the canal lumen in both ears. Gain and phase of horizontal, vertical, and torsional slow-phase eye velocity were determined from three-dimensional eye movement recordings obtained acutely after the plugging operation, as well as in regular intervals up to 10 mo later. 2. Acutely after plugging, horizontal VOR was minimal during yaw rotation with gains of < 0.1 at all frequencies. Horizontal VOR gain gradually increased over time, reaching gains of 0.4-0.5 for yaw oscillations at 1.1 Hz approximately 5 mo after lateral canal inactivation. This response recovery was strongly frequency dependent: horizontal VOR gains were largest at the highest frequency tested and progressively decreased for lower frequencies. Below approximately 0.1 Hz, no consistent horizontal VOR could be elicited even 10 mo after plugging. 3. The frequency-dependent changes in gain paralleled changes in horizontal VOR phase. Below approximately 0.1-0.05 Hz large phase leads were present, similarly as in semicircular canal primary afferents. Smaller phase leads were also present at higher frequencies, particularly at 1.1 Hz (the highest frequency tested). 4. Consistent with the afferent-like dynamics of the adapted horizontal VOR, per- and postrotatory horizontal responses to constant-velocity yaw rotations were short lasting. Time constants of the slow-phase eye velocity envelope of the horizontal postrotatory nystagmus were approximately 2 s. Nonetheless, a consistent horizontal optokinetic afternystagmus was evoked in plugged animals. 5. A torsional component that was absent in intact animals was consistently present during yaw rotation acutely after lateral canal inactivation and remained approximately constant thereafter. The frequency response characteristics of this

This technical paper discusses the following: (1) The VOR of two rhesus monkeys was studied before and after 14 days of spaceflight to determine effects of microgravity on the VOR. Horizontal, vertical and roll eye movements were recorded in these and six other monkeys implanted with scleral search coils. Animals were rotated about a vertical axis to determine the gain of the horizontal, vertical and roll VOR. They were rotated about axes tilted from the vertical (off-vertical axis rotation, OVAR) to determine steady state gains and effects of gravity on modulations in eye position and eye velocity. They were also tested for tilt dumping of post-rotatory nystagmus. (2) The gain of the horizontal VOR was close to unity when animals were tested 15 and 18 hours after flight. VOR gain values were similar to those registered before flight. If the gain of the horizontal VOR changes in microgravity, it must revert to normal soon after landing. (3) Steady state velocities of nystagmus induced by off-vertical axis rotation (OVAR) were unchanged by adaptation to microgravity, and the phase of the modulations was similar before and after flight. However, modulations in horizontal eye velocity had more variation after landing and were on mean about 50% larger for angles of tilt of the axis of rotation between 50 and 90?/s after flight. This difference was similar in both animals and was significant. (4) A striking finding was that tilt dumping was lost in the one animal tested for this function. This loss persisted for several days after return. This is reminiscent of the loss of response to pitch while rotating in the M-131 experiments of Skylab, and must be studied in detail in future spaceflights. (5) Thus, two major findings emerged from these studies: after spaceflight the modulation of horizontal eye velocity was larger during OVAR, and one animal lost its ability to tilt-dump its nystagmus. Both findings are consistent with the postulate that adaptation to microgravity

The bacterium Vibrio ordalii is best known as the causative agent of vibriosis outbreaks in fish and thus recognized for generating serious production losses in aquaculture systems. Here we report for the first time on the isolation and the genome sequencing of phage vB_VorS-PVo5, infectious to Vibrio ordalii ATCC 33509. The features as well as the complete genome sequence and annotation of the Vibrio phage are described; vB_VorS-PVo5 consists of a lineal double stranded DNA totaling ~ 80.6 Kb in length. Considering its ability to lyse Vibrio ordalii ATCC 33509, the phage is likely to gain importance in future aquaculture applications by controlling the pathogen and as such replacing antibiotics as the treatment of choice.

Voluntary active head rotations produced vestibulo-ocular reflex eye movements (VOR) with the subject viewing a fixation target. When this target jumped, the size of the refixation saccades were a function of the ongoing initial velocity of the eye. Saccades made against the VOR were larger in magnitude. Simulation of a reciprocally innervated model eye movement provided results comparable to the experimental data. Most of the experimental effect appeared to be due to linear summation for saccades of 5 and 10 degree magnitude. For small saccades of 2.5 degrees, peripheral nonlinear interaction of state variables in the neuromuscular plant also played a role as proven by comparable behavior in the simulated model with known controller signals.

Using an acute scleral search coil technique for measuring eye position in alert animals we have shown that after UVD the yaw VOR in the guinea pig shows a permanent gain asymmetry. There is a reduced gain during the first 100 ms of brief, high acceleration horizontal head rotations ("yaw head impulses") towards the operated side, but only a small loss in gain for similar rotations towards the intact side. This result confirms that the horizontal E response during the first 100 ms of an abrupt high acceleration head rotation is a clear indicator of the function of the horizontal canal. These results are similar to those in human patients after unilateral acoustic neuroma operations. The asymmetry in response is large shortly after UVD and decreases over time but is permanent.

Uses a parable from a Kafka novel to illustrate and support the premise that language and literature study should be integrated, even in the early stages. Reading short literary works can explain involved language problems better than long explanations, and can also stimulate further literary study. (CHK)

Acoustic stimulation of the vestibular system has been well documented in humans and has been accepted as a useful tool to diagnose vestibular disorders. The goal of this study was to establish an awake and behaving primate model that might be useful for investigating the neural mechanisms underlying acoustic activation of the vestibular system. We recorded sound-evoked eye movements in monkeys while they performed ocular motor tasks. In the first part of the study, an acoustic click (1 ms, 99 to approximately 125 db peak SPL) was delivered to one of the monkeys' ears while they fixated on visual targets of varying eccentricities and viewing distances. Acoustic clicks were found to evoke well-defined biphasic eye velocity responses. For the movement in the horizontal direction, the first eye velocity peaks were always away from the stimulated ear. For the movement in the vertical direction, however, the directions of the first eye velocity peaks varied from monkey to monkey. This variability was difficult to interpret in the absence of torsional measurement. Thus, our analysis in this report was focused on horizontal eye movements. We found that click-evoked eye movements were disjunctive, with larger first horizontal eye velocity peaks from the eye ipsilateral to the stimulated ear (the amplitude ratio was 1.8 +/- 0.3, n=4). The amplitudes of the first horizontal peaks were also linearly correlated with gaze eccentricity and viewing distance. In the second part of the study, we found that a brief tone-pulse (100 ms, 125 db peak SPL) evoked eye movements that exhibited a well-defined frequency tuning with the most effective stimulating frequencies ranging from 1 K to 1.5 KHz. These data demonstrate that the sound-evoked eye movements in behaving monkeys are well defined and reproducible. This paradigm may be useful for studying the neural mechanisms underlying acoustic activation of the vestibular system.

To deduce recommendations for authors which decrease the rejection probability we investigated retrospectively which reasons were mentioned in 1990 by the editorial board of the 'Nederlands Tijdschrift voor Geneeskunde' when it rejected original articles, reviews, clinical lessons and case reports, and whether length of the article, professional status of the first author, most relevant specialism and origin of the article influenced the rejection probability. Out of 547 articles 38% (208) were rejected; case reports were rejected most often (49%), reviews least often (33%). Peer review of original articles was the most thorough, of case studies the least. The most frequent reason for rejection in all categories was 'substantial shortcomings', particularly in the original articles (80%). Rejection of clinical lessons and case studies was relatively often due to criteria concerning the clinical message. Both rejected and accepted articles on average exceeded the length limit. Professional status and specialism were associated with a difference in rejection probability (chi 2, p less than 0.05). Specialists had the lowest rejection probability (31%). Nonspecialists benefited from specialist supervision. Articles originating from non-academic institutions were more often rejected than articles from academic centres. We advise authors to judge their articles by means of the criteria mentioned. Consultation of (methodological) experts, literature data bases, and (or) the editorial board can improve their chances. Non-specialists can benefit from the experience and expertise of specialists. In general, scientific attitude and willingness to alter the article according to editorial advice appear to have beneficial results.

We summarize the early observations of SN 1604 made by Johannes Brunowsky and Johannes Kepler in Prague in October 1604. Quoting from Kepler's two books on this subject ("Gründlicher Bericht" and "De stella nova"), we point out that he compared the supernova with respect to its twinkling with an "exquisite multifaceted diamond" and that he thought this object to be rather something like a newly born (proto-)star than a star in its final phase of evolution, as we would call it today. The twinkling of the star was interpreted by Kepler as intrinsic to it rather than an effect of the Earth's atmosphere.

Further evidence was found for adaptive changes in the vestibular "velocity storage" (VS) component of the vestibuloocular reflex in four shuttle astronauts tested in parabolic flight and before, during, and after a 14-day mission. Nystagmus was recorded during and after 1 min of 120 degrees/s rotation. Gains and time constants were determined by computer analysis. Responses correlated with experience. Two subjects were making their first spaceflight. In parabolic flight, their time constants shortened to an average of 60% of 1 G values, presumably because unfamiliar otolith cues reduced VS. However, after 4-10 days in orbit, their time constants were similar or greater than those preflight, indicating VS recovery. The other two subjects had previously flown in space. Their time constants shortened in orbit to an average of 69% of 1 G values, indicating a persisting reduction of VS. This correlation with spaceflight experience has been seen in 9 of 11 subjects on 3 missions. Head pitch did not significantly "dump" nystagmus as it does on Earth.

... traffic control coordination for aircraft proceeding across the United States--Mexican border. DATES... benefit cross-border navigation. Additionally, fixes are established at the border crossing points...

Describes an instructional project, How to Tell a Foreigner to Berlin the Way,'' designed to give 8th graders practical experience in using English; format based on the text London--People ans Pictures,'' Cornelsen-Velhagen & Klasing, Berlin. (RS)

Diagnosing dizzy patients remains a daunting challenge to the clinician in spite of modern imaging and increasingly sophisticated electrophysiological testing. Here we review the major bedside tests of the vestibulo-ocular reflex and how, when combined with a proper examination of the other eye movement systems, one can arrive at an accurate vestibular diagnosis. PMID:22981296

... coincides with the FAA's aeronautical database. DATES: Effective date 0901 UTC, May 5, 2011. The Director of... with the FAA's aeronautical database. Since this is an administrative change, and does not affect...

The report describes the performance of Doppler very high frequency omnirange ( DVOR ) systems with and without a coaxially located tactical air...navigation (TACAN) antenna. Flight tests were conducted to determine double-sideband DVOR (DSDVOR) and single-sideband DVOR (SSDVOR) system performance for

Theoretically rigorous definitions are derived of such parameters as RF signal path length, phase delay, and phase/frequency stability in a Cassegrainian antenna applicable to a narrow bandwidth channel, as well as algorithms for evaluating these parameters. This work was performed in support of the Voyager spacecraft encounter with Uranus in January 1986. The information was needed to provide Voyager/Uranus radio science researchers with a rotational basis for deciding the best strategy to operate the three antennas involved during the crucial 5-hour occultation period of the encounter. Such recommendations are made at the end of the article.

..., Devils Lake, ND, to support non- radar separation requirements when the restricted area is active. DATES...-radar separation and airway clearance from the newly established R-5402, Devils Lake, ND (77 FR 54860... T- route, in addition to V-170, that would maintain appropriate separation from R-5402. The...

A realistic neural-network model was constructed to simulate production of both the slow-phase and quick-phase components of vestibular nystagmus by incorporating a quick-phase pathway into a previous model of the slow phase. The neurons in the network were modelled by multicompartmental Hodgkin-Huxley-style spiking neurons based on known responses and projections of physiologically identified vestibular neurons. The modelling used the GENESIS software package. The slow-phase network consisted of ganglion and medial vestibular nucleus (MVN) neurons; the latter were constructed using biophysical models of MVN type A and B neurons. The quick-phase network contained several types of bursting cells which have been shown to have major roles in the generation of the quick phase: burster-driver neurons, long-lead burst neurons, pause neurons, excitatory burst neurons and inhibitory burst neurons. Comparison of the output neural responses from the model with guinea pig behavioural responses from the companion paper showed consistency between model and animal data for neuron firing patterns, maximal firing rates, and timing, duration and number of quick phases. Comparisons were made for stable head input and for sinusoidal angular stimuli at a range of frequencies from 0.1 to 2 Hz. Except for data at 0.1 Hz, where the simulation produced one more quick phase per half cycle than the animal data, the number of quick phases was consistent between the model and the animal data. The model was also used to simulate the effects both of unilateral vestibular deafferentation (UVD) and of vestibular compensation after UVD, and the responses in the modelled MVN neurons were affected in a way similar to those measured in guinea pig MVN neurons: the number of quick phases and their timing changed in a similar fashion to that observed in behavioural data.

The macrofauna of a dumping area in the eastern part of the German Bight (North Sea) was investigated in July, August and November, 1978 at five stations situated on a transect including central and peripheral areas of the dumping region. Abundance and biomass (ash free dry weight) of the macrofauna and its variation from July to November were analysed as well as the biomass of different taxa. Molluscs dominated over polychaetes, crustaceans and echinoderms. A positive correlation seemed to exist between mud content and biomass at the peripherally situated stations. In the central sewage sludge area, however, the biomass values were reduced. In late autumn the biomass decreased in the entire area due to the death of Diastylis rathkei, Abra alba and Pectinaria koreni. These species were replaced by the mollusc Nucula turgida and polychaete Nephtys hombergii. In autumn the biomass values also showed a distinct minimum at the central stations.

... terrain and new construction signal interference problems and is planned for decommissioning. An airway... the Order. The FAA has determined that this regulation only involves an established body of technical.... Therefore, this regulation: (1) Is not a ``significant regulatory action'' under Executive Order 12866;...

...-12, and V-508 in the Vicinity of Olathe, KS AGENCY: Federal Aviation Administration (FAA), DOT...-10, V-12, and V-508 in the vicinity of Olathe, KS. The FAA is taking this action to adjust the airway...-508, in the vicinity of Olathe, KS (77 FR 9876), due to the planned decommissioning of the...

...;having general applicability and legal effect, most of which are keyed #0;to and codified in the Code of... was upgraded to a Doppler VOR and redesignated as the Anchorage (TED) VOR. The TED VOR was moved...

... action proposes to amend Class E Airspace at Tuskegee, AL, as the Tuskegee VOR/DME has been... necessary due to the decommissioning of the Tuskegee VOR/DME and cancellation of the VOR approach, and...

Examines a late nineteenth-century Milwaukee (Wisconsin) publication for children and young people as a reflection of German-American middle-class culture of the time, showing how the spirit of the 1848 revolution and the experience of the American Civil War shaped German-American intellectuals and how the ideals of freedom and equality dominated…

... Tuskegee, AL, as the Tuskegee VOR/DME has been decommissioned and airspace reconfiguration is necessary for... reconfiguration is necessary due to the decommissioning of the Tuskegee VOR/DME and cancellation of the...

... portions of VOR Federal airways V-16 and V-202. DATES: Comments must be received on or before June 7, 2012... portions of VOR Federal airways V-16 and V-202 that will be affected by the scheduled decommissioning...

vertical VOR and torsional VOR, both without optokinetic feedback, using velocity step tests. 15. SUBJECT TERMS Vestibulo-ocular reflex, autism 16...characterize in ASD vertical VOR and torsional VOR, both without optokinetic feedback, using velocity step tests. This Final Report covers the period from...Specific Aims 1 and 2 of the proposal. The equipment purchased from Neuro Kinetics, Inc. was not designed for testing vertical or torsional nystagmus

... airspace at the Glasgow VHF Omni-Directional Radio Range/Distance Measuring Equipment (VOR/DME) navigation... the surface, at the Glasgow VOR/DME navigation aid, Glasgow, MT, to accommodate IFR aircraft under... within the scope of that authority as it establishes controlled airspace at the Glasgow VOR/DME,...

... of Manhattan Island, thence north along the west bank of the East River to the LGA VOR/DME 6-mile arc... the LGA VOR/DME 6-mile arc to the north tip of Roosevelt Island. (d) New York Class B airspace Hudson... intersect the Colts Neck VOR/DME 012° radial, thence southwest along the Colts Neck 012° radial to...

.../Distance Measuring Equipment (VOR/DME). This action also would make a minor adjustment to the geographic coordinates of the VOR/DME and make a correction to the regulatory text. DATES: Comments must be received on... vicinity of the Hugo VOR/ DME, CO. The airspace update is necessary due to the decommissioning of the...

... of Manhattan Island, thence north along the west bank of the East River to the LGA VOR/DME 6-mile arc... the LGA VOR/DME 6-mile arc to the north tip of Roosevelt Island. (d) New York Class B airspace Hudson... intersect the Colts Neck VOR/DME 012° radial, thence southwest along the Colts Neck 012° radial to...

... airspace at the Salmon VHF Omni-Directional Radio Range/Distance Measuring Equipment (VOR/DME) navigation... the surface, at the Salmon VOR/DME navigation aid, Salmon, ID, to accommodate IFR aircraft under... within the scope of that authority as it establishes controlled airspace at the Salmon VOR/DME,...

... of Manhattan Island, thence north along the west bank of the East River to the LGA VOR/DME 6-mile arc... the LGA VOR/DME 6-mile arc to the north tip of Roosevelt Island. (d) New York Class B airspace Hudson... intersect the Colts Neck VOR/DME 012° radial, thence southwest along the Colts Neck 012° radial to...

... southwest tip of Manhattan Island, thence north along the west bank of the East River to the LGA VOR/DME 6... River, from the LGA VOR/DME 6-mile arc to the north tip of Roosevelt Island. (d) New York Class B... River to intersect the Colts Neck VOR/DME 012° radial, thence southwest along the Colts Neck 012°...

... of Manhattan Island, thence north along the west bank of the East River to the LGA VOR/DME 6-mile arc... the LGA VOR/DME 6-mile arc to the north tip of Roosevelt Island. (d) New York Class B airspace Hudson... intersect the Colts Neck VOR/DME 012° radial, thence southwest along the Colts Neck 012° radial to...

... at the Rome VHF Omni- Directional Radio Range/Distance Measuring Equipment (VOR/DME) ] navigation aid... the surface, at the Rome VOR/DME navigation aid, Rome, OR, to accommodate IFR aircraft under control... within the scope of that authority as it establishes controlled airspace at the Rome VOR/DME, Rome,...

Vortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in major depressive patients. Here we compared the effects of 14-day treatments with VOR and escitalopram (ESC, selective serotonin reuptake inhibitor) on neuronal activity in the medial prefrontal cortex (mPFC). Ten groups of rats (5 standard, 5 depleted of 5-HT with p-chlorophenylalanine -pCPA-, used as model of cognitive impairment) were fed with control food or with two doses of VOR-containing food. Four groups were implanted with minipumps delivering vehicle or ESC 10 mg/kg·day s.c. The two VOR doses enable occupation by VOR of SERT+5-HT3-R and all targets, respectively, and correspond to SERT occupancies in patients treated with 5 and 20 VOR mg/day, respectively. Putative pyramidal neurons (n = 985) were recorded extracellularly in the mPFC of anesthetized rats. Sub-chronic VOR administration (but not ESC) significantly increased neuronal discharge in standard and 5-HT-depleted conditions, with a greater effect of the low VOR dose in standard rats. VOR increased neuronal discharge in infralimbic (IL) and prelimbic (PrL) cortices. Hence, oral VOR doses evoking SERT occupancies similar to those in treated patients increase mPFC neuronal discharge. The effect in 5-HT-depleted rats cannot be explained by an antagonist action of VOR at 5-HT3-R and suggests a non-canonical interaction of VOR with 5-HT3-R. These effects may underlie the superior pro-cognitive efficacy of VOR compared with SSRIs in animal models.

Whenever the head turns, the vestibuloocular reflex (VOR) produces compensatory eye movements to help stabilize the image of the visual world on the retina. Uncompensated slip of the visual world across the retina results in a gradual change in VOR gain to minimize the image motion. VOR gain changes naturally during normal development and during recovery from neuronal damage. We ask here whether visual slip is necessary for the development of the chicken VOR (as in other species) and whether it is required for the recovery of the VOR after hair cell loss and regeneration. In the first experiment, chickens were reared under stroboscopic illumination, which eliminated visual slip. The horizontal and vertical VORs (h- and vVORs) were measured at different ages and compared with those of chickens reared in normal light. Strobe-rearing prevented the normal development of both h- and vVORs. After 8 wk of strobe-rearing, 3 days of exposure to normal light caused the VORs to recover partially but not to normal values. In the second experiment, 1-wk-old chicks were treated with streptomycin, which destroys most vestibular hair cells and reduces hVOR gain to zero. In birds, vestibular hair cells regenerate so that after 8 wk in normal illumination they appear normal and hVOR gain returns to values that are normal for birds of that age. The treated birds in this study recovered in either normal or stroboscopic illumination. Their hVOR and vVOR and vestibulocollic reflexes (VCR) were measured and compared with those of untreated, age-matched controls at 8 wk posthatch, when hair cell regeneration is known to be complete. As in previous studies, the gain of the VOR decreased immediately to zero after streptomycin treatment. After 8 wk of recovery under normal light, the hVOR was normal, but vVOR gain was less than normal. After 8 wk of recovery under stroboscopic illumination, hVOR gain was less than normal at all frequencies. VCR recovery was not affected by the strobe

The coconut kernel residues obtained after extraction of coconut milk (MR) and virgin coconut oil (VOR) were analysed for their potential as dietary fibres. VOR was defatted and treated chemically using three solvent systems to isolate coconut cell wall polysaccharides (CCWP). Nutritional composition of VOR, MR and CCWPs indicated that crude fibre, neutral detergent fibre, acid detergent fibre and hemicelluloses contents were higher in CCWPs than in VOR and MR. MR contained a notably higher content of fat than VOR and CCWPs. The oil holding capacity, water holding capacity and swelling capacity were also higher in CCWPs than in VOR and MR. All the isolates and MR and VOR had high metal binding capacities. The CCWPs when compared with commercially available fibre isolates, indicated improved dietary fibre properties. These results show that chemical treatment of coconut kernel by-products can enhance the performance of dietary fibre to yield a better product.

Argues that the usefulness of strictly quantitative research is still questioned in educational studies, primarily due to deficiencies in methodological training. Uses a critique of a recent study by Heitmeyer et al. (1995) to illustrate the requirements of "good" empirical research. Considers the problems of hypothesis testing in field research.…

Unpaced voluntary horizontal head oscillation was used to study the Vestibulo-Ocular Reflex (VOR) on Shuttle flights STS 7 and 8. Ten subjects performed head oscillations at 0.33 Hz + or - 30 deg amplitude under the followng conditions: VVOR (visual VOR), eyes open and fixed on a stationary target; VOR-EC, with eyes closed and fixed on the same target in imagination; and VOR-S (VOR suppression), with eyes open and fixed on a head-synchronized target. Effects of weightlessness, flight phase, and Space Motion Sickness (SMS) on head oscillation characteristics were examined. A significant increase in head oscillation frequency was noted inflight in subjects free from SMS. In subjects susceptible to SMS, frequency was reduced during their Symptomatic period. The data also suggest that the amplitude and peak velocity of head oscillation were reduced early inflight. No significant changes were noted in reflex gain or phase in any of the test conditions; however, there was a suggestion of an increase in VVOR and VOR-ES gain early inflight in asymptomatic subjects. A significant difference in VOR-S was found between SMS susceptible and non-susceptible subjects. There is no evidence that any changes in VOR characteristics contributed to SMS.

We habituated the dominant time constant of the horizontal vestibuloocular reflex (VOR) of rhesus and cynomolgus monkeys by repeated testing with steps of velocity about a vertical axis and adapted the gain of the VOR by altering visual input with magnifying and reducing lenses. After baseline values were established, the nodulus and ventral uvula of the vestibulocerebellum were ablated in two monkeys, and the effects of nodulouvulectomy and flocculectomy on VOR gain adaptation and habituation were compared. The VOR time constant decreased with repeated testing, rapidly at first and more slowly thereafter. The gain of the VOR was unaffected. Massed trials were more effective than distributed trials in producing habituation. Regardless of the schedule of testing, the VOR time constant never fell below the time constant of the semicircular canals (approximately 5 s). This finding indicates that only the slow component of the vestibular response, the component produced by velocity storage, was habituated. In agreement with this, the time constant of optokinetic after-nystagmus (OKAN) was habituated concurrently with the VOR. Average values for VOR habituation were obtained on a per session basis for six animals. The VOR gain was adapted by natural head movements in partially habituated monkeys while they wore x 2.2 magnifying or x 0.5 reducing lenses. Adaptation occurred rapidly and reached about +/- 30%, similar to values obtained using forced rotation. VOR gain adaptation did not cause additional habituation of the time constant. When the VOR gain was reduced in animals with a long VOR time constant, there were overshoots in eye velocity that peaked at about 6-8 s after the onset or end of constant-velocity rotation. These overshoots occurred at times when the velocity storage integrator would have been maximally activated by semicircular canal input. Since the activity generated in the canals is not altered by visual adaptation, this finding indicates that the gain

Objective According to a recent randomized, double-blind clinical trial comparing the combination of voriconazole and anidulafungin (VOR+ANI) with VOR monotherapy for invasive aspergillosis (IA) in patients with hematologic disease or with hematopoietic stem cell transplant, mortality was lower after 6 weeks with VOR+ANI than with VOR monotherapy in a post hoc analysis of patients with galactomannan-based IA. The objective of this study was to compare the cost-effectiveness of VOR+ANI with VOR, from the perspective of hospitals in the Spanish National Health System. Methods An economic model with deterministic and probabilistic analyses was used to determine costs per life-year gained (LYG) for VOR+ANI versus VOR in patients with galactomannan-based IA. Mortality, adverse event rates, and life expectancy were obtained from clinical trial data. The costs (in 2015 euros [€]) of the drugs and the adverse event-related costs were obtained from Spanish sources. A Tornado plot and a Monte Carlo simulation (1,000 iterations) were used to assess uncertainty of all model variables. Results According to the deterministic analysis, for each patient treated with VOR+ANI compared with VOR monotherapy, there would be a total of 0.348 LYG (2.529 vs 2.181 years, respectively) at an incremental cost of €5,493 (€17,902 vs €12,409, respectively). Consequently, the additional cost per LYG with VOR+ANI compared with VOR would be €15,785. Deterministic sensitivity analyses confirmed the robustness of these findings. In the probabilistic analysis, the cost per LYG with VOR+ANI was €15,774 (95% confidence interval: €15,763–16,692). The probability of VOR+ANI being cost-effective compared with VOR was estimated at 82.5% and 91.9%, based on local cost-effectiveness thresholds of €30,000 and €45,000, respectively. Conclusion According to the present economic study, combination therapy with VOR+ANI is cost-effective as primary therapy of IA in galactomannan

Changes in the vestibulo-ocular reflex (VOR) during space flight have been suspected of contributing to space motion sickness. The horizontal VOR was studied in nine subjects on two space shuttle missions. Active unpaced head oscillation at 0.3 Hz was used as the stimulus to examine the gain and phase of the VOR with and without visual input, as well as the visual suppression of the reflex. No statistically significant changes were noted inflight in the gains or phase shifts of the VOR during any test condition, or between space motion sickness susceptible and nonsusceptible populations. Although VOR suppression was unaffected by spaceflight, the space motion sickness-susceptible group tended to exhibit greater error in the suppression than the nonsusceptible group. It is concluded that at this stimulus frequency, VOR gain is unaffected by space-flight, and any minor individual changes do not seem to contribute to space motion sickness.

The horizontal vestibulo-ocular reflex (VOR) during transient, high-acceleration (1900-7100 deg/sec-squared) head rotations was studied in four human subjects. Such stimuli perturbed the angle of gaze and caused illusory movement of a viewed target (oscillopsia). The disturbance of gaze could be attributed to the latency of the VOR (which ranged from 6-15 ms) and inadequate compensatory eye rotations (median VOR gain ranged from 0.61-0.83).

Prevailing evidence indicates a relatively late life decline in human vestibulo-ocular reflex (VOR) function. Although mice are commonly used in mechanistic studies of vestibular function, it remains unclear whether aging produces a corresponding decline in VOR function in mice. We sought to determine how the baseline VOR and its short-term adaptation were affected by aging. We tested 8 young (3-month old) and 8 aged (30-month old-equivalent to a ∼80-year old human) C57BL/6 mice. We measured their VOR response to whole-body static tilts and during 0.1-10 Hz whole-body sinusoidal and transient rotations before and after VOR adaptation training. Our data revealed minimal differences in static counter-tilt response between young and aged mice, but a significant deficit in baseline VOR gain in aged mice during transient rotations. Moreover, aged mice had a significant decrease in short-term VOR adaptation, particularly for training that sought to decrease the VOR response.

The vestibulo-ocular response (VOR) may not be fully developed in children with an intellectual and developmental disability (IDD). This study aimed to identify the presence of VOR deficit in children and young adults with unspecified mild-to-moderate intellectual and developmental disability and its effect on balance control. Twenty-one children…

... aircraft using a new VHF Omni-Directional Radio Range (VOR) Standard Instrument Approach Procedure (SIAP) at Gallatin Field Airport. This action would enhance the safety and management of aircraft operations... necessary to accommodate aircraft using the new VOR SIAP's at Gallatin Field Airport, Bozeman, MT....

... airspace at the Gillette VHF Omni-Directional Radio Range/Distance Measuring Equipment (VOR/DME), Gillette... the surface, at the Gillette VOR/DME navigation aid, Gillette, WY, to accommodate IFR aircraft under... within the scope of that authority as it establishes controlled airspace at the Gillette...

... Range/Distance Measuring Equipment (VOR/DME), Localizer Type Directional Aid/Distance Measuring Equipment (LDA/DME) Standard Instrument Approach Procedures (SIAPs) at the new airport. This will improve... more than was needed for the SIAP, and modified portions for the VOR/DME SIAP by reducing the amount...

Translational vestibulo-ocular reflexes (trVORs) are characterized by distinct spatio-temporal properties and sensitivities that are proportional to the inverse of viewing distance. Anodal (inhibitory) labyrinthine stimulation (100 microA, < 2 s) during motion decreased the high-pass filtered dynamics, as well as horizontal trVOR sensitivity and its dependence on viewing distance. Cathodal (excitatory) currents had opposite effects. Translational VORs were also affected after unilateral labyrinthectomy. Animals lost their ability to modulate trVOR sensitivity as a function of viewing distance acutely after the lesion. These deficits partially recovered over time, albeit a significant reduction in trVOR sensitivity as a function of viewing distance remained in compensated animals. During fore-aft motion, the effects of unilateral labyrinthectomy were more dramatic. Both acute and compensated animals permanently lost their ability to modulate fore-aft trVOR responses as a function of target eccentricity. These results suggest that (1) the dynamics and viewing distance-dependent properties of the trVORs are very sensitive to changes in the resting firing rate of vestibular afferents and, consequently, vestibular nuclei neurons; (2) the most irregularly firing primary otolith afferents that are most sensitive to labyrinthine electrical stimulation might contribute to reflex dynamics and sensitivity; (3) inputs from both labyrinths are necessary for the generation of the translational VORs.

The dynamic response properties of horizontal vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) were characterized in 216 human subjects ranging in age from 7 to 81 years. The object of this cross-sectional study was to determine the effects of aging on VOR and OKR reflex dynamics, and to identify the distributions of parameters which describe VOR and OKR responses to pseudorandom stimuli in a putatively normal population. In general, VOR and OKR response parameters changed in a manner consistent with declining function with increasing age. For the VOR this was reflected in declining response amplitudes, although the magnitude of the decline was small relative to the variability of the data. For the OKR the lag time of the response, probably associated with the time required for visual information processing, increased linearly with age at a rate of about 1 ms per year.

In Xenopus laevis tadpoles, effects of asymmetrical light conditions on the roll-induced vestibuloocular reflex (rVOR) were tested for the developmental period between stage 47 and 49. For comparison, the rVOR was tested in dim- and high-symmetrical light environments. Test parameters were the rVOR gain and rVOR amplitude. Under all light conditions, the rVOR increased from tadpole stage 47 to 49. For all stages, the asymmetrical light field induced the strongest response, the dim light field the weakest one. The response for the left and right eye was identical, even if the tadpoles were tested under asymmetrical light conditions. The experiments can be considered as hints (1) for an age-dependent light sensitivity of vestibular neurons, and (2) for the existence of control systems for coordinated eye movements that has its origin in the proprioceptors of the extraocular eye muscles.

Although cerebellar mechanisms are vital to maintain accuracy during complex movements and to calibrate simple reflexes, recent in vitro studies have called into question the widely held view that synaptic changes within cerebellar pathways exclusively guide alterations in motor performance. Here we investigate the vestibulo-ocular reflex (VOR) circuitry by applying temporally precise activation of vestibular afferents in awake-behaving monkeys to link plasticity at different neural sites with changes in motor performance. Behaviourally relevant activation patterns produce rapid attenuation of direct pathway VOR neurons, but not their nerve input. Changes in the strength of this pathway are sufficient to induce a lasting decrease in the evoked VOR. In addition, indirect brainstem pathways display complementary nearly instantaneous changes, contributing to compensating for the reduced sensitivity of primary VOR neurons. Taken together, our data provide evidence that multiple sites of plasticity within VOR pathways can rapidly shape motor performance in vivo. PMID:27157829

Our goal is to review vestibulo-oculomotor reflex (VOR) studies on several peripheral vestibular disorders (Ménière’s disease, vestibular neuritis, benign paroxysmal positional vertigo, superior canal dehiscence syndrome, and vestibular neuroma), using the scleral search coil (SSC) technique. Head movements are detected by vestibular receptors and the elicited VOR is responsible for compensatory 3 dimensional eye movements. Therefore, to study the VOR it is necessary to assess the direction and velocity of 3 dimensional head, and eye movements. This can be achieved using the SSC technique. Interaction between a scleral search coil and an alternating magnetic field generates an electrical signal that is proportional to eye position. Ideally, eye rotation axis is aligned with head rotation axis and VOR gain (eye velocity/head velocity) for horizontal and vertical head rotations is almost 1. The VOR gain, however, for torsional head rotations is smaller and about 0.7. PMID:17683700

The goal of the present study was to determine if adaptive modulation of vestibulo-ocular reflex (VOR) function is associated with commensurate alterations in manual target localization. To measure the effects of adapted VOR on manual responses we developed the Vestibular-Contingent Pointing Test (VCP). In the VCP test, subjects pointed to a remembered target following passive whole body rotation in the dark. In the first experiment, subjects performed VCP before and after wearing 0.5X minifying lenses that adaptively attenuate horizontal VOR gain. Results showed that adaptive reduction in horizontal VOR gain was accompanied by a commensurate change in VCP performance. In the second experiment, bilaterally labyrinthine deficient (LD) subjects were tested to confirm that vestibular cues were central to the spatial coding of both eye and hand movements during VCP. LD subjects performed significantly worse than normal subjects. These results demonstrate that adaptive change in VOR can lead to alterations in manual target localization.

At present, voriconazole (VOR) is the drug of first choice for treating invasive pulmonary aspergillosis (IPA). However, particularly in advanced stages of disease and in the severely immunocompromised host, the mortality remains substantial. The combination of VOR with an echinocandin may improve the therapeutic outcome. We investigate here whether combining VOR and anidulafungin (ANI) in advanced IPA in transiently neutropenic rats results in a higher therapeutic efficacy. Since VOR is metabolized more rapidly in rodents than in humans, dosage adjustment for VOR is necessary to obtain an area under the plasma concentration-time curve (AUC) in rodents that is equivalent to that of humans. In this study, the pharmacokinetics of VOR and ANI in rats were elucidated, and dosage schedules were applied that produced AUCs similar to those of humans. The developed dose schedules were well tolerated by the rats, without effects on renal and hepatic functions. VOR showed excellent efficacy in early IPA (100% rat survival). In advanced IPA, VOR was less efficacious (50% rat survival), whereas a significant decrease in galactomannan concentrations in lungs and sera was found in surviving rats. ANI administered in advanced IPA resulted in 22% rat survival, and the serum concentrations of fungal galactomannan were slightly but not significantly decreased. The addition of ANI to VOR did not result in significantly increased therapeutic efficacy in advanced IPA, resulting in 67% rat survival and a significant decrease in galactomannan concentration in serum. In conclusion, VOR monotherapy is therapeutically effective in the treatment of advanced-stage IPA and superior to the use of ANI. Combining both agents does not significantly improve the therapeutic outcome.

Vestibular velocity storage enhances the efficacy of the angular vestibulo-ocular reflex (VOR) during relatively low-frequency head rotations. This function is modulated by GABA-mediated inhibitory cerebellar projections. Velocity storage also exists in perceptual pathway and has similar functional principles as VOR. However, it is not known whether the neural substrate for perception and VOR overlap. We propose two possibilities. First, there is the same velocity storage for both VOR and perception; second, there are nonoverlapping neural networks: one might be involved in perception and the other for the VOR. We investigated these possibilities by measuring VOR and perceptual responses in healthy human subjects during whole-body, constant-velocity rotation steps about all three dimensions (yaw, pitch, and roll) before and after 10 mg of 4-aminopyridine (4-AP). 4-AP, a selective blocker of inward rectifier potassium conductance, can lead to increased synchronization and precision of Purkinje neuron discharge and possibly enhance the GABAergic action. Hence 4-AP could reduce the decay time constant of the perceived angular velocity and VOR. We found that 4-AP reduced the decay time constant, but the amount of reduction in the two processes, perception and VOR, was not the same, suggesting the possibility of nonoverlapping or partially overlapping neural substrates for VOR and perception. We also noted that, unlike the VOR, the perceived angular velocity gradually built up and plateau prior to decay. Hence, the perception pathway may have additional mechanism that changes the dynamics of perceived angular velocity beyond the velocity storage. 4-AP had no effects on the duration of build-up of perceived angular velocity, suggesting that the higher order processing of perception, beyond the velocity storage, might not occur under the influence of mechanism that could be influenced by 4-AP. PMID:22777507

Stimulus deprivation or stimulus augmentation can induce long-lasting modifications to sensory and motor systems. If deprivation is effective only during a limited period of life this phase is called "critical period." A critical period was described for the development of the roll-induced vestibuloocular reflex (rVOR) of Xenopus laevis using spaceflights. Spaceflight durations and basic conditions of Xenopus' development did not make it possible to answer the question whether exposure of the immature vestibular organ to weightlessness affects rVOR development. The embryonic development of Pleurodeles waltl is slow enough to solve this problem because the rVOR cannot be induced before 15 dpf. Stage 20-21 embryos (4 dpf) were exposed to microgravity during a 10-day spaceflight, or to 3g hypergravity following the same time schedule. After termination of altered gravity, the rVOR was recorded twice in most animals. The main observations were as follows: (1) after the first rVOR appearance at stage 37 (16 dpf), both rVOR gain and amplitude increased steadily up to saturation levels of 0.22 and 20°, respectively. (2) Three days after termination of microgravity, flight and ground larvae showed no rVOR; 1 day later, the rVOR could be induced only in ground larvae. Differences disappeared after 3 weeks. (3) For 10 days after 3g exposure, rVOR development was similar to that of 1g-controls but 3 weeks later, 3g-larvae showed a larger rVOR than 1g-controls. These observations indicate that the immature vestibular system is transiently sensitive to microgravity exposure and that exposure of the immature vestibular system to hypergravity leads to a slowly growing vestibular sensitization.

Changes in the horizontal vestibulo-ocular reflex (VOR) in darkness were investigated in naive cats during: (1) repeated sessions of angular velocity steps, (2) one continuous 1-h session of sinusoidal oscillations at 0.01, 0.02, 0.04, or 0.12 Hz, and (3) repeated sessions of 1-h sinusoidal oscillations at 0.02 and 0.04 Hz. Before and after each vestibular training, the VOR response parameters elicited by both velocity steps and sinusoidal oscillations were measured in order to evaluate the transfer of habituation from one stimulus to the other. After training with velocity steps, the amplitude and duration of the VOR to velocity steps decreased by about 67% and 52%, respectively. This vestibular habituation transferred to the VOR response generated by sinusoidal oscillations, since a decrease in VOR gain was observed at 0.02 and 0.04 Hz, and an increase in phase lead was observed at 0.02, 0.04, and 0.08 Hz. After 1 h exposure to sinusoidal oscillations, the VOR gain was only reduced by 21-28%, whereas VOR phase lead decreased. The same changes were observed during subsequent sessions, with no retention of the response decrements from one session to the next. At the end of sinusoidal training, the amplitude of the VOR generated by velocity steps was slightly altered. After sinusoidal training, the weak changes in the VOR gain accompanied by a decrease in the VOR phase lead, and the absence of retention of these effects from one session to the next, suggest these changes are not characteristics of a vestibular habituation. Previous reports of vestibular habituation induced by repeated sinusoidal oscillations may be confounded by the fact that the angular velocity steps used for quantifying the effects may have been responsible for this habituation.

To maintain visual fixation on a distant target during head rotation, the angular vestibulo-ocular reflex (aVOR) should rotate the eyes at the same speed as the head and in exactly the opposite direction. However, in primates for which the 3-dimensional (3D) aVOR has been extensively characterised (humans and squirrel monkeys (Saimiri sciureus)), the aVOR response to roll head rotation about the naso-occipital axis is lower than that elicited by yaw and pitch, causing errors in aVOR magnitude and direction that vary with the axis of head rotation. In other words, primates keep the central part of the retinal image on the fovea (where photoreceptor density and visual acuity are greatest) but fail to keep that image from twisting about the eyes' resting optic axes. We tested the hypothesis that aVOR direction dependence is an adaptation related to primates' frontal-eyed, foveate status through comparison with the aVOR of a lateral-eyed, afoveate mammal (Chinchilla lanigera). As chinchillas' eyes are afoveate and never align with each other, we predicted that the chinchilla aVOR would be relatively low in gain and isotropic (equal in gain for every head rotation axis). In 11 normal chinchillas, we recorded binocular 3D eye movements in darkness during static tilts, 20–100 deg s−1 whole-body sinusoidal rotations (0.5–15 Hz), and 3000 deg s−2 acceleration steps. Although the chinchilla 3D aVOR gain changed with both frequency and peak velocity over the range we examined, we consistently found that it was more nearly isotropic than the primate aVOR. Our results suggest that primates' anisotropic aVOR represents an adaptation to their forward-eyed, foveate status. In primates, yaw and pitch aVOR must be compensatory to stabilise images on both foveae, whereas roll aVOR can be under-compensatory because the brain tolerates torsion of binocular images that remain on the foveae. In contrast, the lateral-eyed chinchilla faces different adaptive demands and thus

Abstract Calibration of the vestibulo-ocular reflex (VOR) depends on the presence of visual feedback. However, the cellular mechanisms associated with VOR modifications at the level of the brainstem remain largely unknown. A new protocol was designed to expose freely behaving mice to a visuo-vestibular mismatch during a 2-week period. This protocol induced a 50% reduction of the VOR. In vivo pharmacological experiments demonstrated that the VOR reduction depends on changes located outside the flocculus/paraflocculus complex. The cellular mechanisms associated with the VOR reduction were then studied in vitro on brainstem slices through a combination of vestibular afferent stimulation and patch-clamp recordings of central vestibular neurons. The evoked synaptic activity demonstrated that the efficacy of the synapses between vestibular afferents and central vestibular neurons was decreased. In addition, a long-term depression protocol failed to further decrease the synapse efficacy, suggesting that the VOR reduction might have occurred through depression-like mechanisms. Analysis of the intrinsic membrane properties of central vestibular neurons revealed that the synaptic changes were supplemented by a decrease in the spontaneous discharge and excitability of a subpopulation of neurons. Our results provide evidence that a long-lasting visuo-vestibular mismatch leads to changes in synaptic transmission and intrinsic properties of central vestibular neurons in the direct VOR pathway. Overall, these results open new avenues for future studies on visual and vestibular interactions conducted in vivo and in vitro. PMID:28303261

An alkyl polyglycoside (APG) surfactant was used in ultrasonic-assisted extraction to effectively extract vitexin-2″-O-rhamnoside (VOR) and vitexin (VIT) from Crataegus pinnatifida leaves. APG0810 was selected as the surfactant. The extraction process was optimized for ultrasonic power, the APG concentration, ultrasonic time, soaking time, and liquid-solid ratio. The proposed approach showed good recovery (99.80-102.50% for VOR and 98.83-103.19% for VIT) and reproducibility (relative standard deviation, n=5; 3.7% for VOR and 4.2% for VIT) for both components. The proposed sample preparation method is both simple and effective. The use of APG for extraction of key herbal ingredients shows great potential. Ten widely used commercial macroporous resins were evaluated in a screening study to identify a suitable resin for the separation and purification of VOR and VIT. After comparing static and dynamic adsorption and desorption processes, HPD100B was selected as the most suitable resin. After column adsorption and desorption on this resin, the target compounds VOR and VIT can be effectively separated from the APG0810 extraction solution. Recoveries of VOR and VIT were 89.27%±0.42% and 85.29%±0.36%, respectively. The purity of VOR increased from 35.0% to 58.3% and the purity of VIT increased from 12.5% to 19.9%.

Background. A single dose of the histone deacetylase inhibitor vorinostat (VOR) up-regulates HIV RNA expression within resting CD4+ T cells of treated, aviremic human immunodeficiency virus (HIV)–positive participants. The ability of multiple exposures to VOR to repeatedly disrupt latency has not been directly measured, to our knowledge. Methods. Five participants in whom resting CD4+ T-cell–associated HIV RNA (rc-RNA) increased after a single dose of VOR agreed to receive daily VOR Monday through Wednesday for 8 weekly cycles. VOR serum levels, peripheral blood mononuclear cell histone acetylation, plasma HIV RNA single-copy assays, rc-RNA, total cellular HIV DNA, and quantitative viral outgrowth assays from resting CD4+ T cells were assayed. Results. VOR was well tolerated, with exposures within expected parameters. However, rc-RNA measured after dose 11 (second dose of cycle 4) or dose 22 (second dose of cycle 8) increased significantly in only 3 of the 5 participants, and the magnitude of the rc-RNA increase was much reduced compared with that after a single dose. Changes in histone acetylation were blunted. Results of quantitative viral outgrowth and other assays were unchanged. Conclusions. Although HIV latency is disrupted by an initial VOR dose, the effect of subsequent doses in this protocol was much reduced. We hypothesize that the global effect of VOR results in a refractory period of ≥24 hours. The optimal schedule for VOR administration is still to be defined. PMID:24620025

The vestibulo-ocular reflex (VOR) consists of two intermingled non-linear subsystems; namely, nystagmus and saccade. Typically, nystagmus is analysed using a single sufficiently long signal or a concatenation of them. Saccade information is not analysed and discarded due to insufficient data length to provide consistent and minimum variance estimates. This paper presents a novel sparse matrix approach to system identification of the VOR. It allows for the simultaneous estimation of both nystagmus and saccade signals. We show via simulation of the VOR that our technique provides consistent and unbiased estimates in the presence of output additive noise.

The vestibulo-ocular reflex (VOR) of five patients with surgically confirmed unilateral peripheral vestibular lesions is evaluated. Testing used both earth vertical axis (EVA) and earth horizontal axis (EHA) yaw rotation. Results indicated that the patients had short VOR time constants, asymmetric responses to both EVA and EHA rotation, and normal EHA modulation components. These findings suggest that unilateral peripheral vestibular loss causes a shortened VOR time constant even with the addition of dynamic otolithic stimulation and causes an asymmetry in semicircular canal-ocular reflexes and one aspect of otolith-ocular reflexes.

Coordinates 7-18 7-7 Aeroflot Flight Zone OMEGA Accuracies vs DME or DME /VOR Coordinates 7-18 7-8 Alabama Getty Measurements 7-20 7-9 British Respect...navigation equipment on board the aircraft during the tests consisted of TAC.N VOR/ DME , sextant and a driftmeter. The majority of flight hours were...measurement of two (2) distances from DME , or azimuth and distance for VOR/ DME with distances from the radio beacons of not more than 40 KM. During the

1. The effects of constant anodal currents (100 microA) delivered bilaterally to both labyrinths on the horizontal vestibuloocular response (VOR) were studied in squirrel monkeys during steps of angular velocity in the dark. We report that bilateral anodal currents decreased eye velocity approximately 30-50% during the period of galvanic stimulation without a change in the time constant of VOR. The decrease in eye velocity, present during steps of angular velocity, was not observed during sinusoidal head rotation at 0.2, 0.5, and 1 Hz. The results suggest that responses from irregular vestibular afferents influence VOR amplitude during constant velocity rotation.

WIRES has been used to predict bearing errors experienced by aircraft and caused by wire obstacles in the field of an airport VOR/ DVOR station (87]. In...by the presence of metallic bodies of revolution near VOR/ DVOR airport stations [87]. 60 The original body-of-revolution code is on deposit with the...34Effects of Scattering by Obstacles in the Field of VOR/ DVOR ," Report No. FAA-RD-74-153, Syracuse University- FAA; Sept. 1974. 88. H. Gruenberg

It was hypothesized that the absence of the gravitational reference cues may be responsible for adaptive changes in the vestibulo-ocular reflex (VOR). These changes result in the alteration of the direction of the compensatory slow phase (SP) eye movements in microgravity. In order to test this hypothesis, the direction of the VOR SP relative to head motion was investigated in three astronauts during and after an eight-day orbital flight by passive sinusoidal pitch or yaw angular motion at two frequencies. The results of the inflight and postflight testing are considered. The observed deviation between VOR SP and head motion suggests that spatial transformation in the VOR occurred during adaptation to microgravity. It is considered that, although this spatial transformation might be due to a sensory bias, it may reflect central changes in the reference system used for spatial orientation in microgravity.

Communications Switching System (ICSS). In addition to the ICSS, AFSS personnel have direct voice interface with VOR equipment to provide emergency voice...FSDPS supports the AFSS work station which is combined in various configurations to support the different AFSS operational positions. Direct voice ... interface in the form of emergency messages are transmitted over the VOR in the same manner as the facility voice identification. NASSRS Requirement

We investigated the interaction of smooth ocular pursuit (SP) and the vestibulo-ocular reflex (VOR) during horizontal, combined eye-head tracking (CEHT) in patients with abnormalities of either the VOR or SP movements. Our strategy was to apply transient stimuli that capitalized on the different latencies to onset of SP and the VOR. During CEHT of a target moving at 15 deg/sec, normal subjects and patients with VOR deficits all tracked the target with a gain close to 1.O. When the heads of normal subjects were suddenly and unexpectedly braked to a halt during CEHT, the eye promptly began to move in the orbit to track the target, but eye-in-orbit velocity transiently fell to about 60-70% of target velocity. In patients with deficient labyrinthine function, following the onset of the head brake, eye movements to track the target were absent, and SP movements were not generated until about 100 msec later. In patients with deficient SP, CEHT was superior to SP tracking with the head stationary; after the onset of the head brake, tracking eye movements were initiated promptly, but eye velocity was less than 50% of target velocity and increased only slightly thereafter. These results indicate that at least two mechanisms operate to overcome the VOR and allow gaze to track the target during CEHT: (1) the SP system provides a signal to cancel a normally-operating VOR (this cancellation signal is not needed by labyrinthine-deficient patients who have no VOR to cancel), and (2) a reduction of the gain of the VOR is achieved, an ability that is preserved even in patients with cerebral lesions that impair SP.

The vestibulo-ocular reflexes (VOR) are determined not only by angular acceleration, but also by the presence of gravity and linear acceleration. This phenomenon was studied by measuring three-dimensional nystagmic eye movements, with implanted search coils, in four male squirrel monkeys. Monkeys were rotated in the dark at 200 degrees/s, centrally or 79 cm off-axis, with the axis of rotation always aligned with gravity and the spinal axis of the upright monkeys. The monkey's position relative to the centripetal acceleration (facing center or back to center) had a dramatic influence on the VOR. These studies show that a torsional response was always elicited that acted to shift the axis of eye rotation toward alignment with gravito-inertial force. On the other hand, a slow phase downward vertical response usually existed, which shifted the axis of eye rotation away from the gravito-inertial force. These findings were consistent across all monkeys. In another set of tests, the same monkeys were rapidly tilted about their interaural (pitch) axis. Tilt orientations of 45 degrees and 90 degrees were maintained for 1 min. Other than a compensatory angular VOR during the rotation, no consistent eye velocity response was ever observed during or following the tilt. The absence of any response following tilt proves that the observed torsional and vertical responses were not a positional nystagmus. Model simulations qualitatively predict all components of these eccentric rotation and tilt responses. These simulations support the conclusion that the VOR during eccentric rotation may consist of two components: a linear VOR and a rotational VOR. The model predicts a slow phase downward, vertical, linear VOR during eccentric rotation even though there was never a change in the force aligned with monkey's spinal (Z) axis. The model also predicts the torsional components of the response that shift the rotation axis of the angular VOR toward alignment with gravito-inertial force.

We characterized the dependence of motor learning in the monkey vestibulo-ocular reflex (VOR) on the duration, frequency, and relative timing of the visual and vestibular stimuli used to induce learning. The amplitude of the VOR was decreased or increased through training with paired head and visual stimulus motion in the same or opposite directions, respectively. For training stimuli that consisted of simultaneous pulses of head and target velocity 80-1000 msec in duration, brief stimuli caused small changes in the amplitude of the VOR, whereas long stimuli caused larger changes in amplitude as well as changes in the dynamics of the reflex. When the relative timing of the visual and vestibular stimuli was varied, brief image motion paired with the beginning of a longer vestibular stimulus caused changes in the amplitude of the reflex alone, but the same image motion paired with a later time in the vestibular stimulus caused changes in the dynamics as well as the amplitude of the VOR. For training stimuli that consisted of sinusoidal head and visual stimulus motion, low-frequency training stimuli induced frequency-selective changes in the VOR, as reported previously, whereas high-frequency training stimuli induced changes in the amplitude of the VOR that were more similar across test frequency. The results suggest that there are at least two distinguishable components of motor learning in the VOR. One component is induced by short-duration or high-frequency stimuli and involves changes in only the amplitude of the reflex. A second component is induced by long-duration or low-frequency stimuli and involves changes in the amplitude and dynamics of the VOR.

The effects of altered gravitational forces (AGF) on the development of the static vestibulo-ocular reflex (VOR) were investigated in Xenopus laevis tadpoles exposed to hypergravity (1.4g; 3g) or microgravity conditions (German spacelab mission D-2) for 9-10 days. The effects of light conditions during development were also tested by exposing tadpoles to either complete darkness (DD) or 12:12 h light-dark conditions (LD). The static VOR was induced by lateral roll. The efficacy of the VOR circuit after termination of AGF conditions was described by the peak-to-peak amplitude of the sinusoidal VOR characteristics (i.e. amplitude). The static VOR was first observed at stage 41 for both LD and DD tadpoles. Its further development was retarded in the DD tadpoles compared with the LD tadpoles up to stage 48. Microgravity as well as hypergravity exposure caused a significant (P < 0.05, at least) decrease in the static VOR amplitude during the first week after termination of the AGF period. The decreases were 39.4% in the microgravity group, 16.2% in the 1.4g group and 24.9-42.9% in the 3g group compared with the 1g ground-reared siblings at the same developmental stages. The response deficits usually disappeared but persisted for at least 2 weeks in animals whose development was retarded by hypergravity exposure. It is postulated (i) that gravity exerts an important influence on the normal development of the roll-induced static VOR; (ii) that hypergravity exposure decreases the sensitivity of the gravity-sensitive system so that recordings under 1g conditions cause a weaker static VOR; and (iii) that the vestibulo-spinal pathway possesses a higher degree of plasticity than the vestibulo-ocular pathway.

Background Voriconazole (VOR) levels are highly variable, with potential implications to both efficacy and safety. We hypothesized that VOR therapeutic drug monitoring (TDM) will decrease the incidence of treatment failures and adverse events (AEs). Methods We initiated a prospective, randomized, non-blinded multicenter study to compare clinical outcomes in adult patients randomized to standard dosing (clinician-driven) vs. TDM (doses adjusted based on levels). VOR trough levels were obtained on day 5, 14, 28, and 42 (or at completion of drug; ± 3 days). Real-time dose adjustments were made to maintain a range between 1–5 μg/mL on the TDM-arm, while levels were assessed retrospectively in the standard arm. Patient questionnaires were administered to assess subjective AEs. Results The study was discontinued prematurely, after 29 patients were enrolled. Seventeen (58.6%) patients experienced 38 AEs: visual changes (22/38, 57.9%), neurological symptoms (13/38, 34.2%), and liver abnormalities (3/38, 7.9%). VOR was discontinued in 7 (25%) patients because of an AE (4 standard-arm, 3 TDM-arm). VOR levels were frequently out of range in the standard-arm (8 tests >5 μg/mL; 9 tests < 1 μg/mL). Three dose changes occurred in the TDM-arm for VOR levels <1 μg/mL. Levels decreased over time in the standard-arm, with mean VOR levels lower at end of therapy compared to TDM (1.3 vs. 4.6 μg/mL, P = 0.008). Conclusions VOR TDM has become widespread clinical practice, based on known variability in drug levels, which impaired accrual in this study. Although comparative conclusions are limited, observations of variability and waning levels over time support TDM. PMID:26346408

Reduction of the dominant time constant (T(VOR)) of the angular vestibulo-ocular reflex (aVOR) by habituation is associated with a decrease in motion sickness susceptibility. Baclofen, a GABA(b) agonist, reduces the time constant of the velocity storage integrator in the aVOR in a dose-dependent manner. The high frequency aVOR gain is unaltered by baclofen. Here we demonstrate that the reduction in T(VOR) produced by oral administration of 20 mg of baclofen causes a significant reduction in motion sickness susceptibility, tested with roll while rotating (RWR). These data show that motion sickness susceptibility can be pharmacologically manipulated with a GABA(b) agonist and support our conclusion that motion sickness is generated through velocity storage. We also show how baclofen acts on velocity storage at the neural level. A vestibular-plus-saccade (VPS) neuron was recorded in the rostral medial vestibular nucleus (rMVN) of a cynomolgus monkey, an area where we postulate that velocity storage is generated. The cell had a time constant during steps of velocity that was close to that of the T(VOR). After parenteral administration of baclofen, there was a similar decrease in the time constants of the VPS neuron and the T(VOR). This is the first demonstration of the concurrence of unit and aVOR time constants before and after baclofen. The data support the hypothesis that the velocity storage integrator is generated through activity of vestibular-only (VO) and VPS neurons in rMVN and suggest that GABA(b) synapses on VO and VPS neurons are likely to be involved in the baclofen-induced reduction in motion sickness susceptibility.

Conventional views of the Vestibulo-Ocular Reflex (VOR) have emphasized testing with caloric stimuli and by passively rotating patients at low frequencies in a chair. The properties of the VOR tested under these conditions differ from the performance of this reflex during the natural function for which it evolved-locomotion. Only the VOR (and not visually mediated eye movements) can cope with the high-frequency angular and linear perturbations of the head that occur during locomotion; this is achieved by generating eye movements at short latency (less than 16 msec). Interpretation of vestibular testing is enhanced by the realization that, although the di- and trisynaptic components of the VOR are essential for this short-latency response, the overall accuracy and plasticity of the VOR depend upon a distributed, parallel network of neurons involving the vestibular nuclei. Neurons in this network variously encode inputs from the labyrinthine semicircular canals and otoliths, as well as from the visual and somatosensory systems. The central vestibular pathways branch to contact vestibular cortex (for perception) and the spinal cord (for control of posture). Thus, the vestibular nuclei basically coordinate the stabilization of gaze and posture, and contribute to the perception of verticality and self-motion. Consequently, brainstem disorders that disrupt the VOR cause not just only nystagmus, but also instability of posture (eg, increased fore-aft sway in patients with downbeat nystagmus) and disturbance of spatial orientation (eg, tilt of the subjective visual vertical in Wallenberg's syndrome).

A new vestibulo-ocular reflex (VOR) recording system was developed, which consists of an infrared eye camera, a small velocity sensor and a frequency modulator. Using this system, the head velocity signal was frequency modulated and simultaneously recorded as a sound signal on the audio track of a Hi8 video recorder with eye images. This device enabled recording of the VOR response in routine vestibular clinical practice. The reliability and effectiveness of this system were estimated by recording and analysing the VOR response against manually controlled rotation in normal subjects (n = 22) and in patients with unilateral severe vestibular hypofunction (n = 11). VOR gain on clockwise rotation viewed from the top was defined as R gain, and counterclockwise rotation as L gain. Directional preponderance (DP%) was also calculated. VOR gain towards the diseased side was significantly lower than that towards the intact side, and also significantly lower than that of normal subjects. DP% of unilateral vestibular hypofunction cases was significantly larger than that of normal subjects. These findings indicate that this VOR recording system reliably detects severe unilateral vestibular hypofunction.

The effects of altered gravitational conditions (AGC) on the development of the static vestibulo-ocular reflex (VOR) and readaptation to 1g were investigated in the amphibian Xenopus laevis. Tadpoles were exposed to microgravity (μg) during the German Space Mission D-2 for 10 days, using the STATEX closed survival system, or to 3g for 9 days during earth-bound experiments. At the beginning of AGC, the tadpoles had not yet developed the static VOR. The main results were: (i) Tadpoles with ug- or 3g-experience had a lower gain of the static VOR than the 1g-controls during the 2nd and 5th post-AGC days, (ii) Readaptation to response levels of 1g-reared controls usually occurred during the following weeks, except in slowly developing tadpoles with 3g-experience. Readaptation was less pronounced if, during the acute VOR test, tadpoles were rolled from the inclined to the normal posture than in the opposite test situation. It is postulated that (i) gravity is necessarily involved in the development of the static VOR, but only during a period including the time before onset of the first behavioural response; and (ii) readaptation which is superimposed by the processes of VOR development depends on many factors including the velocity of development, the actual excitation level of the vestibular systems and the neuroplastic properties of its specific pathways.

The effects of altered gravitational conditions (AGC) on the development of the static vestibulo-ocular reflex (VOR) and readaptation to 1g were investigated in the amphibian Xenopus laevis. Tadpoles were exposed to microgravity during the German Space Mission D-2 for 10 days, using the STATEX closed survival system, or to 3g for 9 days during earth-bound experiments. At the beginning of AGC, the tadpoles had not yet developed the static VOR. The main results were: (i) Tadpoles with microgravity- or 3g-experience had a lower gain of the static VOR than the 1g-controls during the 2nd and 5th post-AGC days. (ii) Readaptation to response levels of 1g-reared controls usually occurred during the following weeks, except in slowly developing tadpoles with 3g-experience. Readaptation was less pronounced if, during the acute VOR test, tadpoles were rolled from the inclined to the normal posture than in the opposite test situation. It is postulated that (i) gravity is necessarily involved in the development of the static VOR, but only during a period including the time before onset of the first behavioural response; and (ii) readaptation which is superimposed by the processes of VOR development depends on many factors including the velocity of development, the actual excitation level of the vestibular systems and the neuroplastic properties of its specific pathways.

Ménière's attack has been shown to temporarily alter the vestibuloocular reflex (VOR). A patient with unilateral Ménière's disease was serially evaluated with the video Head Impulse Test during single, untreated episodes of acute vertigo. Spontaneous nystagmus activity was concurrently recorded in order to establish the three typical phases of Ménière's attack (irritative, paralytic, and recovery) and correlate them with VOR performance. The onset of attack was associated with a quick change in VOR gain on the side of the affected ear. While a rapidly progressive reduction of the VOR was evident at the paralytic nystagmus phase, in the recovery phase the VOR gain returned to normal and the direction of the previous nystagmus reversed. The membrane rupture potassium intoxication theory provides a good foundation with which to explain these dynamic VOR changes and the observed triphasic direction behavior of the spontaneous nystagmus. We additionally postulated that endolymphatic fluid displacement could have a synergic effect during the earliest phase of attack. PMID:28018691

1. The dynamic contribution of otolith signals to three-dimensional angular vestibuloocular reflex (VOR) was studied during off-vertical axis rotations in rhesus monkeys. In an attempt to separate response components to head velocity from those to head position relative to gravity during low-frequency sinusoidal oscillations, large oscillation amplitudes were chosen such that peak-to-peak head displacements exceeded 360 degrees. Because the waveforms of head position and velocity differed in shape and frequency content, the particular head position and angular velocity sensitivity of otolith-ocular responses could be independently assessed. 2. During both constant velocity rotation and low-frequency sinusoidal oscillations, the otolith system generated two different types of oculomotor responses: 1) modulation of three-dimensional eye position and/or eye velocity as a function of head position relative to gravity, as presented in the preceding paper, and 2) slow-phase eye velocity as a function of head angular velocity. These two types of otolith-ocular responses have been analyzed separately. In this paper we focus on the angular velocity responses of the otolith system. 3. During constant velocity off-vertical axis rotations, a steady-state nystagmus was elicited that was maintained throughout rotation. During low-frequency sinusoidal off-vertical axis oscillations, dynamic otolith stimulation resulted primarily in a reduction of phase leads that characterize low-frequency VOR during earth-vertical axis rotations. Both of these effects are the result of an internally generated head angular velocity signal of otolithic origin that is coupled through a low-pass filter to the VOR. No change in either VOR gain or phase was observed at stimulus frequencies larger than 0.1 Hz. 4. The dynamic otolith contribution to low-frequency angular VOR exhibited three-dimensional response characteristics with some quantitative differences in the different response components. For

A recent study showed that the angular vestibulo-ocular reflex (VOR) can be better adaptively increased using an incremental retinal image velocity error signal compared with a conventional constant large velocity-gain demand (×2). This finding has important implications for vestibular rehabilitation that seeks to improve the VOR response after injury. However, a large portion of vestibular patients have unilateral vestibular hypofunction, and training that raises their VOR response during rotations to both the ipsilesional and contralesional side is not usually ideal. We sought to determine if the vestibular response to one side could selectively be increased without affecting the contralateral response. We tested nine subjects with normal vestibular function. Using the scleral search coil and head impulse techniques, we measured the active and passive VOR gain (eye velocity / head velocity) before and after unilateral incremental VOR adaptation training, consisting of self-generated (active) head impulses, which lasted ≈ 15 min. The head impulses consisted of rapid, horizontal head rotations with peak-amplitude 15°, peak-velocity 150°/s and peak-acceleration 3,000°/s(2). The VOR gain towards the adapting side increased after training from 0.92 ± 0.18 to 1.11 ± 0.22 (+22.7 ± 20.2 %) during active head impulses and from 0.91 ± 0.15 to 1.01 ± 0.17 (+11.3 ± 7.5 %) during passive head impulses. During active impulses, the VOR gain towards the non-adapting side also increased by ≈ 8 %, though this increase was ≈ 70 % less than to the adapting side. A similar increase did not occur during passive impulses. This study shows that unilateral vestibular adaptation is possible in humans with a normal VOR; unilateral incremental VOR adaptation may have a role in vestibular rehabilitation. The increase in passive VOR gain after active head impulse adaptation suggests that the training effect is robust.

1. We used a modeling approach to test the hypothesis that, in humans, the smooth pursuit (SP) system provides the primary signal for cancelling the vestibuloocular reflex (VOR) during combined eye-head tracking (CEHT) of a target moving smoothly in the horizontal plane. Separate models for SP and the VOR were developed. The optimal values of parameters of the two models were calculated using measured responses of four subjects to trials of SP and the visually enhanced VOR. After optimal parameter values were specified, each model generated waveforms that accurately reflected the subjects' responses to SP and vestibular stimuli. The models were then combined into a CEHT model wherein the final eye movement command signal was generated as the linear summation of the signals from the SP and VOR pathways. 2. The SP-VOR superposition hypothesis was tested using two types of CEHT stimuli, both of which involved passive rotation of subjects in a vestibular chair. The first stimulus consisted of a "chair brake" or sudden stop of the subject's head during CEHT; the visual target continued to move. The second stimulus consisted of a sudden change from the visually enhanced VOR to CEHT ("delayed target onset" paradigm); as the vestibular chair rotated past the angular position of the stationary visual stimulus, the latter started to move in synchrony with the chair. Data collected during experiments that employed these stimuli were compared quantitatively with predictions made by the CEHT model. 3. During CEHT, when the chair was suddenly and unexpectedly stopped, the eye promptly began to move in the orbit to track the moving target. Initially, gaze velocity did not completely match target velocity, however; this finally occurred approximately 100 ms after the brake onset. The model did predict the prompt onset of eye-in-orbit motion after the brake, but it did not predict that gaze velocity would initially be only approximately 70% of target velocity. One possible

Human horizontal rotational vestibulo-ocular reflex (rVOR) has been extensively investigated: the horizontal semicircular canals sense yaw rotations with high-pass filter dynamics and a time constant (TC) around 5 s, yet the rVOR response shows a longer TC due to a central processing stage, known as velocity storage mechanism (VSM). It is generally assumed that the vertical rVOR behaves similarly to the horizontal one; however, VSM processing of the human vertical rVOR is still to be proven. We investigated the vertical rVOR in eight healthy human subjects using three experimental paradigms: (1) per- and post-rotatory around an earth-vertical axis (ear down rotations, EDR), (2) post-rotatory around an earth-horizontal axis with different stopping positions (static otolith stimulation), (3) per-rotatory around an earth-horizontal axis (dynamic otolith stimulation). We found that the TC of vertical rVOR responses ranged 3-10 s, depending both on gravity and on the direction of rotation. The shortest TC were found in response to post-rotatory earth-horizontal stimulation averaging 3.6 s, while they were prolonged in EDR stimulation, i.e. when the head angular velocity vector is aligned with gravity, with a mean value of about 6.0 s. Overall, the longest TC were observed in per-rotatory earth-horizontal stimulation, averaging 7.8 s. The finding of longer TC in EDR than in post-rotatory earth-horizontal stimulation indicates a role for the VSM in the vertical rVOR, although its contribution appears to be weaker than on the horizontal rVOR and may be directionally asymmetric. The results from per-rotatory earth-horizontal stimulation, instead, imply a role for the otoliths in controlling the duration of the vertical rVOR response. We found no reorientation of the response toward earth horizontal, indicating a difference between human and monkey rVOR.

Parallel pathways mediate the rotatory vestibuloocular reflex (VOR). If the VOR undergoes adaptive modification with spectacles that change the magnification of the visual scene, signals in one neural pathway are modified, whereas those in another are not. By recording the responses of vestibular afferents and abducens neurons for vestibular oscillations at frequencies from 0.5 to 50 Hz, we have elucidated how vestibular signals are processed in the modified versus unmodified VOR pathways. For the small stimuli we used (±15°/s), the afferents with the most regular spontaneous discharge fired throughout the cycle of oscillation even at 50 Hz, whereas afferents with more irregular discharge showed phase locking. For all afferents, the firing rate was in phase with stimulus head velocity at low frequencies and showed progressive phase lead as frequency increased. Sensitivity to head velocity increased steadily as a function of frequency. Abducens neurons showed highly regular spontaneous discharge and very little evidence of phase locking. Their sensitivity to head velocity during the VOR was relatively flat across frequencies; firing rate lagged head velocity at low frequencies and shifted to large phase leads as stimulus frequency increased. When afferent responses were provided as inputs to a two-pathway model of the VOR, the output of the model reproduced the responses of abducens neurons if the unmodified and modified VOR pathways had frequency-dependent internal gains and included fixed time delays of 1.5 and 9 ms. The phase shifts predicted by the model provide fingerprints for identifying brain stem neurons that participate in the modified versus unmodified VOR pathways. PMID:16760348

Vorinostat (VOR) has been reported to enhance the cytotoxic effects of doxorubicin (DOX) with fewer side effects because of the lower DOX dosage in breast cancer cells. In this study, we investigated the novel mechanism underlying the synergistic cytotoxic effects of VOR and DOX co-treatment in cervical cancer cells HeLa, CaSki and SiHa cells. Co-treatment with VOR and DOX at marginal doses led to the induction of apoptosis through caspase-3 activation, poly (ADP-ribose) polymerase cleavage and DNA micronuclei. Notably, the synergistic growth inhibition induced by the co-treatment was attributed to the upregulation of the pro-apoptotic protein Bad, as the silencing of Bad expression using small interfering RNA (siRNA) abolished the phenomenon. As siRNA against p53 did not result in an increase in acetylated p53 and the consequent upregulation of Bad, the observed Bad upregulation was mediated by acetylated p53. Moreover, a chromatin immunoprecipitation analysis showed that the co-treatment of HeLa cells with VOR and DOX increased the recruitment of acetylated p53 to the bad promoter, with consequent bad transactivation. Conversely, C33A cervical cancer cells containing mutant p53 co-treated with VOR and DOX did not exhibit Bad upregulation, acetylated p53 induction or consequent synergistic growth inhibition. Together, the synergistic growth inhibition of cervical cancer cell lines induced by co-treatment with VOR and DOX can be attributed to the upregulation of Bad, which is induced by acetylated p53. These results show for the first time that the acetylation of p53, rather than histones, is a mechanism for the synergistic growth inhibition induced by VOR and DOX co-treatments.

Self-motion perception and the vestibulo-ocular reflex (VOR) were investigated in healthy subjects during asymmetric whole body yaw plane oscillations while standing on a platform in the dark. Platform oscillation consisted of two half-sinusoidal cycles of the same amplitude (40°) but different duration, featuring a fast (FHC) and a slow half-cycle (SHC). Rotation consisted of four or 20 consecutive cycles to probe adaptation further with the longer duration protocol. Self-motion perception was estimated by subjects tracking with a pointer the remembered position of an earth-fixed visual target. VOR was measured by electro-oculography. The asymmetric stimulation pattern consistently induced a progressive increase of asymmetry in motion perception, whereby the gain of the tracking response gradually increased during FHCs and decreased during SHCs. The effect was observed already during the first few cycles and further increased during 20 cycles, leading to a totally distorted location of the initial straight-ahead. In contrast, after some initial interindividual variability, the gain of the slow phase VOR became symmetric, decreasing for FHCs and increasing for SHCs. These oppositely directed adaptive effects in motion perception and VOR persisted for nearly an hour. Control conditions using prolonged but symmetrical stimuli produced no adaptive effects on either motion perception or VOR. These findings show that prolonged asymmetric activation of the vestibular system leads to opposite patterns of adaptation of self-motion perception and VOR. The results provide strong evidence that semicircular canal inputs are processed centrally by independent mechanisms for perception of body motion and eye movement control. These divergent adaptation mechanisms enhance awareness of movement toward the faster body rotation, while improving the eye stabilizing properties of the VOR.

Previous studies have reported that the translational vestibuloocular reflex (TVOR) follows a three-dimensional (3D) kinematic behavior that is more similar to visually guided eye movements, like pursuit, rather than the rotational VOR (RVOR). Accordingly, TVOR rotation axes tilted with eye position toward an eye-fixed reference frame rather than staying relatively fixed in the head like in the RVOR. This difference arises because, contrary to the RVOR where peripheral image stability is functionally important, the TVOR like pursuit and saccades cares to stabilize images on the fovea. During most natural head and body movements, both VORs are simultaneously activated. In the present study, we have investigated in rhesus monkeys the 3D kinematics of the combined VOR during yaw rotation about eccentric axes. The experiments were motivated by and quantitatively compared with the predictions of two distinct hypotheses. According to the first (fixed-rule) hypothesis, an eye-position-dependent torsion is computed downstream of a site for RVOR/TVOR convergence, and the combined VOR axis would tilt through an angle that is proportional to gaze angle and independent of the relative RVOR/TVOR contributions to the total eye movement. This hypothesis would be consistent with the recently postulated mechanical constraints imposed by extraocular muscle pulleys. According to the second (image-stabilization) hypothesis, an eye-position-dependent torsion is computed separately for the RVOR and the TVOR components, implying a processing that takes place upstream of a site for RVOR/TVOR convergence. The latter hypothesis is based on the functional requirement that the 3D kinematics of the combined VOR should be governed by the need to keep images stable on the fovea with slip on the peripheral retina being dependent on the different functional goals of the two VORs. In contrast to the fixed-rule hypothesis, the data demonstrated a variable eye-position-dependent torsion for the

The dynamic response properties of horizontal vestibulo-ocular reflex (VOR) were characterized in 216 human subjects ranging in age from 7 to 81 years. The object of this cross-sectional study was to determine the effects of aging on VOR dynamics, and to identify the distributions of parameters which describe VOR responses to caloric and to sinusoidal rotational stimuli in a putatively normal population. Caloric test parameters showed no consistent trend with age. Rotation test parameters showed declining response amplitude and slightly less compensatory response phase with increasing age. The magnitudes of these changes were not large relative to the variability within the population. The age-related trends in VOR were not consistent with the anatomic changes in the periphery reported by others which showed an increasing rate of peripheral hair cell and nerve fiber loss in subjects over 55 years. The poor correlation between physiological and anatomical data suggest that adaptive mechanisms in the central nervous system are important in maintaining the VOR.

Unitary activities of 288 neurons were recorded extracellularly in the medial vestibular nucleus (MV) in anesthetized cats. In 19 neurons, located in the rostral part of the MV adjacent to the stria acustica, floccular middle zone stimulation resulted in cessation of spontaneous discharges. Systematic microstimulation in the brainstem during recording of 16 of 19 target neurons of floccular middle zone inhibition revealed that the target neurons projected to the ipsilateral abducens nucleus (ABN), and not to the contralateral ABN nor the oculomotor nucleus. The conjugate ipsilateral horizontal eye movement elicited by middle zone stimulation may be mediated by this pathway to motoneurons and internuclear neurons in the ipsilateral ABN. In additional experiments, the MV neurons responding antidromically to ipsilateral ABN stimulation and orthodromically to ipsilateral 8 nerve stimulation were recorded extracellularly. In only 7 of 36 recorded neurons, middle zone stimulation depressed the orthodromic and spontaneous activities. Many neurons were free of floccular inhibition. As to the route of floccular inhibitory control over the vestibulo-ocular reflex (VOR) during visual-vestibular stimulation, we propose that the interaction of target and VOR relay neurons takes place at the ipsilateral ABN and modulates the VOR, in addition to well known Ito's proposal that the interaction of the floccular output and the VOR takes place at secondary vestibular neurons and modulates the VOR.

Living with an uncompensated, abnormal vestibular system requires oppressive modification of life style and often prevents return to work and activities of daily living. Patients with vestibular abnormalities were studied to determine the minimal residual vestibular function required to achieve compensation. Three groups of patients with (a) complete unilateral loss of vestibular function with normal horizontal canal-vestibulo-ocular (HCVOR) function in the opposite ear, (b) complete unilateral loss with abnormal HCVOR function in the opposite ear, and (c) bilateral reduction of vestibular function from aminoglycoside toxicity underwent vestibuloocular (VOR), optokinetic (OKN), visual-VOR (VVOR), and computerized dynamic posturography (CDP) tests before and after therapeutic procedures. Results suggest that a minimal VOR response amplitude must be present for compensation of VVOR function to occur. The roles of VOR and OKN phase shifts in vestibular compensation are more complicated and require further study. Compensation of vestibulospinal function does not necessarily accompany VOR or VVOR compensation. Ascending and descending vestibular compensatory mechanisms may involve different spatial sensory inputs. Results of these studies have important implications for the diagnosis and treatment of patients with vestibular disorders, including selection and monitoring of patients for therapeutic regimens such as vestibular nerve section and streptomycin therapy.

Young fish ( Oreochromis mossambicus) were exposed to microgravity (μg) for 9 to 10 days, or to hypergravity (hg) for 9 days. For several weeks after termination of μg and hg, the roll-induced static vestibuloocular reflex (rVOR) was recorded. In stage 11/12-fish, the rVOR amplitude (angle between the maximal up and down movement of an eye during a complete 360° lateral roll) of μg-animals increased significantly by 25% compared to 1g-controls during the first post-flight week but decreased to the control level during the second post-flight week. Microgravity had no effect in stage 14/16 fish on the rVOR amplitude. After 3g-exposure, the rVOR amplitude was significantly reduced for both groups compared to their 1g-controls. Readaptation to 1g-condition was completed during the second post-3g week. We postulate a critical period during which the development of the macular vestibuloocular reflex depends on gravitational input, and which is limited by the first appearence of the rVOR. At this period of early development, exposure to microgravity sensitizes the vestibular system while hypergravity desensitizes it.

A new algorithm (VOR-MFS) is presented for the solution of a generalized Hamiltonian model of point vortex dynamics in an arbitrary two-dimensional computational domain. The VOR-MFS algorithm utilizes the method of fundamental solutions (MFS) to obtain an approximation to the model Hamiltonian by solution of an appropriate boundary value problem. Unlike standard point vortex methods, VOR-MFS requires knowledge only of the free-space (R2) Green's function for the problem as opposed to the domain-adapted Green's function, permitting solution of a much wider range of problems. VOR-MFS is first validated against a vortex image model for the case of (2D Euler) multiple vortex motion in both circular and 'Neumann-oval' shaped domains. It is then demonstrated that VOR-MFS can solve for quasi-geostrophic shallow water point vortex motion in the same domains. The exponential convergence of the MFS method is shown to lead to good conservation properties for each of the solutions presented.

The gain of the vestibulo-ocular reflex (VOR) normally depends on the distance between the subject and the visual target, but it remains uncertain whether vergence angle can be linked to changes in VOR gain through a process of context-dependent adaptation. In this study, we examined this question with an adaptation paradigm that modified the normal relationship between vergence angle and retinal image motion. Subjects were rotated sinusoidally while they viewed an optokinetic (OKN) stimulus through either diverging or converging prisms. In three subjects the diverging prisms were worn while the OKN stimulus moved out of phase with the head, and the converging prisms were worn when the OKN stimulus moved in-phase with the head. The relationship between the vergence angle and OKN stimulus was reversed in the fourth subject. After 2 h of training, the VOR gain at the two vergence angles changed significantly in all of the subjects, evidenced by the two different VOR gains that could be immediately accessed by switching between the diverged and converged conditions. The results demonstrate that subjects can learn to use vergence angle as the contextual cue that retrieves adaptive changes in the angular VOR.

Young fish (Oreochromis mossambicus) were exposed to microgravity (micro g) for 9 to 10 days, or to hypergravity (hg) for 9 days. For several weeks after termination of micro g and hg, the roll-induced static vestibuloocular reflex (rVOR) was recorded. In stage 11/12-fish, the rVOR amplitude (angle between the maximal up and down movement of an eye during a complete 360 degree lateral roll) of micro g-animals increased significantly by 25% compared to 1 g-controls during the first post-flight week but decreased to the control level during the second post-flight week. Microgravity had no effect in stage 14/16 fish on the rVOR amplitude. After 3 g-exposure, the rVOR amplitude was significantly reduced for both groups compared to their 1 g-controls. Readaptation to 1 g-condition was completed during the second post-3 g week. We postulate a critical period during which the development of the macular vestibuloocular reflex depends on gravitational input, and which is limited by the first appearance of the rVOR. At this period of early development, exposure to microgravity sensitizes the vestibular system while hypergravity desensitizes it.

Background Chiari type II malformation (CII) is a developmental anomaly of the cerebellum and brainstem, which are important structures for processing the vestibulo-ocular reflex (VOR). We investigated the effects of the deformity of CII on the angular VOR during active head motion. Methods Eye and head movements were recorded using an infrared eye tracker and magnetic head tracker in 20 participants with CII [11 males, age range 8-19 years, mean (SD) 14.4 (3.2) years]. Thirty-eight age-matched healthy children and adolescents (21 males) constituted the control group. Participants were instructed to ‘look’ in darkness at the position of their thumb, placed 25 cm away, while they made horizontal and vertical sinusoidal head rotations at frequencies of about 0.5 Hz and 2 Hz. Parametric and non-parametric tests were used to compare the two groups. Results The VOR gains, the ratio of eye to head velocities, were abnormally low in two participants with CII and abnormally high in one participant with CII. Conclusion The majority of participants with CII had normal VOR performance in this investigation. However, the deformity of CII can impair the active angular VOR in some patients with CII. Low gain is attributed to brainstem damage and high gain to cerebellar dysfunction. PMID:18973069

Normal subjects are able to change voluntarily and continuously their head-eye latency together with their compensatory eye movement gain. A continuous spectrum of intent-latency modes of the subject's coordinated gaze through verbal feedback could be demonstrated. It was also demonstrated that the intent to counteract any perturbation of head-eye movement, i.e., the mental set, permitted the subjects to manipulate consciously their vestibular ocular reflex (VOR) gain. From the data, it is inferred that the VOR is always on. It may be, however, variably suppressed by higher cortical control. With appropriate training, head-mounted displays should permit an easy VOR presetting that leads to image stabilization, perhaps together with a decrease of possible misjudgements.

The effects of deficient labyrinthine function on smooth visual tracking with the eyes and head were investigated, using ten patients with bilateral peripheral vestibular disease and ten normal controls. Active, combined eye-head tracking (EHT) was significantly better in patients than smooth pursuit with the eyes alone, whereas normal subjects pursued equally well in both cases. Compensatory eye movements during active head rotation in darkness were always less in patients than in normal subjects. These data were used to examine current hypotheses that postulate central cancellation of the vestibulo-ocular reflex (VOR) during EHT. A model that proposes summation of an integral smooth pursuit command and VOR/compensatory eye movements is consistent with the findings. Observation of passive EHT (visual fixation of a head-fixed target during en bloc rotation) appears to indicate that in this mode parametric gain changes contribute to modulation of the VOR.

Eye-head motion was studied pre-, in- and postflight during single voluntary head turns. A transient increase in vestibulo-ocular reflex (VOR) gain occurred early in the flight, but later trended toward normal. This increased gain was produced by a relative increase in eye counterrotation velocity. Asymmetries in gain with right and left turns also occurred, caused by asymmetries in eye counterrotation velocities. These findings were remarkably similar to those from Soviet primate studies using gaze fixation targets, except the human study trended more rapidly toward normal. These findings differ substantially from those measuring VOR gain by head oscillation, in which no significant changes were found inflight. No visual disturbances were noted in either test condition or in normal activities. These head turn studies are the only ones to date documenting any functional change in VOR in weightlessness.

Grassland birds are declining at a faster rate than any other group of North American bird species. Livestock grazing is the primary economic use of grasslands in the western United States, but the effects of this use on distribution and productivity of grassland birds are unclear. We examined nest density and success of ground-nesting birds on grazed and ungrazed grasslands in western Montana. In comparison to grazed plots, ungrazed plots had reduced forb cover, increased litter cover, increased litter depth, and increased visual obstruction readings (VOR) of vegetation. Nest density among 10 of 11 common bird species was most strongly correlated with VOR of plots, and greatest nest density for each species occurred where mean VOR of the plot was similar to mean VOR at nests. Additionally, all bird species were relatively consistent in their choice of VOR at nests despite substantial differences in VOR among plots. We suggest that birds selected plots based in part on availability of suitable nest sites and that variation in nest density relative to grazing reflected the effect of grazing on availability of nest sites. Nest success was similar between grazed plots and ungrazed plots for two species but was lower for nests on grazed plots than on ungrazed plots for two other species because of increased rates of predation, trampling, or parasitism by brown-headed cowbirds (Molothrus ater). Other species nested almost exclusively on ungrazed plots (six species) or grazed plots (one species), precluding evaluation of the effects of grazing on nest success. We demonstrate that each species in a diverse suite of ground-nesting birds preferentially used certain habitats for nesting and that grazing altered availability of preferred nesting habitats through changes in vegetation structure and plant species composition. We also show that grazing directly or indirectly predisposed some bird species to increased nesting mortality. Management alternatives that avoid

Although anatomically well described, the functional role of the mammalian efferent vestibular system (EVS) remains unclear. Unlike in fish and reptiles, the mammalian EVS does not seem to play a role in modulation of primary afferent activity in anticipation of active head movements. However, it could play a role in modulating long-term mechanisms requiring plasticity such as vestibular adaptation. We measured the efficacy of vestibuloocular reflex (VOR) adaptation in α9-knockout mice. These mice carry a missense mutation of the gene encoding the α9 nicotinic acetylcholine receptor (nAChR) subunit. The α9 nAChR subunit is expressed in the vestibular and auditory periphery, and its loss of function could compromise peripheral input from the predominantly cholinergic EVS. We measured the VOR gain (eye velocity/head velocity) in 26 α9-knockout mice and 27 cba129 control mice. Mice were randomly assigned to one of three groups: gain-increase adaptation (1.5×), gain-decrease adaptation (0.5×), or no adaptation (baseline, 1×). After adaptation training (horizontal rotations at 0.5 Hz with peak velocity 20°/s), we measured the sinusoidal (0.2–10 Hz, 20–100°/s) and transient (1,500–6,000°/s2) VOR in complete darkness. α9-Knockout mice had significantly lower baseline gains compared with control mice. This difference increased with stimulus frequency (∼5% <1 Hz to ∼25% >1 Hz). Moreover, vestibular adaptation (difference in VOR gain of gain-increase and gain-decrease adaptation groups as % of gain increase) was significantly reduced in α9-knockout mice (17%) compared with control mice (53%), a reduction of ∼70%. Our results show that the loss of α9 nAChRs moderately affects the VOR but severely affects VOR adaptation, suggesting that the EVS plays a crucial role in vestibular plasticity. PMID:26424577

Conventional views of the vestibulo-ocular reflex (VOR) have emphasized testing with caloric stimuli and by passively rotating patients at low frequencies in a chair. The properties of the VOR tested under these conditions differ from the performance of this reflex during the natural function for which it evolved--locomotion. Only the VOR (and not visually mediated eye movements) can cope with the high-frequency angular and linear perturbations of the head that occur during locomotion; this is achieved by generating eye movements at short latency (< 16 msec). Interpretation of vestibular testing is enhanced by the realization that, although the di- and trisynaptic components of the VOR are essential for this short-latency response, the overall accuracy and plasticity of the VOR depend upon a distributed, parallel network of neurons involving the vestibular nuclei. Neurons in this network variously upon a distributed, parallel network of neurons involving the vestibular nuclei. Neurons in this network variously encode inputs from the labyrinthine semicircular canals and otoliths, as well as from the visual and somatosensory systems. The central vestibular pathways branch to contact vestibular cortex (for perception) and the spinal cord (for control of posture). Thus, the vestibular nuclei basically coordinate the stabilization of gaze and posture, and contribute to the perception of verticality and self-motion. Consequently, brainstem disorders that disrupt the VOR cause not just only nystagmus, but also instability of posture (eg, increased fore-aft sway in patients with downbeat nystagmus) and disturbance of spatial orientation (eg, tilt of the subjective visual vertical in Wallenberg's syndrome).

The vestibulo-ocular reflex (VOR) is mediated by integration of canal and otolith inputs to generate compensatory eye movements during head movements. We hypothesized that adaptive change in vestibular processing of gravitoinertial cues would be reflected by plane specific modification of the VOR during passive whole-body rotation during and after spaceflight. Using a repeated measures design, the VOR was assessed in four payload crewmembers in yaw, pitch and roll planes during multiple sessions before, during and after an 8 day orbital mission (STS-42). Rotation was about an earth-vertical axis during ground tests, with the head located off-axis by up to 45cm during pitch and roll rotation (peak acceleration less than 0.2g). The motion profiles included sum-of-sinusoids between 0.02 - 1.39 Hz (yaw), single sinusoids between 0.05-1.25 Hz (yaw and pitch) and velocity steps (yaw, pitch and roll). Eye movements were recorded with both video and electro-oculographic techniques. As expected, VOR gain changes were greater in pitch than in yaw. During pitch rotation, there was a progressive shift in the axis of eye movements during the flight, which was also present during the early post-flight period. This increased horizontal component during pitch, most prevalent at 0.2 Hz, was interpreted as an increase in a translational vergence response elicited during eccentric rotation as subjects imagined a wall fixed target. There was also an increased horizontal component during the eccentric roll step runs performed on flight day 7. These results are consistent with a frequency-dependent increase in otolith-mediated translational VOR responses following adaptation to microgravity. We conclude that the adaptive changes in the VOR are likely to be greatest in the frequency range where there is a cross-over of otolith-mediated tilt and translation responses.

The angular vestibulo-ocular reflex (aVOR) and optokinetic nystagmus (OKN) were elicited simultaneously at low frequencies to study effects of habituation of the velocity storage time constant in the vestibular system on motion sickness. Twenty-nine subjects, eleven of whom were susceptible to motion sickness from common transportation, were habituated by sinusoidal rotation at 0.017 Hz at peak velocities from 5 to 20°/s, while they watched a full-field OKN stimulus. The OKN stripes rotated in the same direction and at the same frequency as the subjects, but at a higher velocity. This produced an OKN opposite in direction to the aVOR response. Motion sickness sensitivity was evaluated with off-vertical axis rotation (OVAR) and by the response to transportation before and after 5 days of visual-vestibular habituation. Habituation did not induce motion sickness or change the aVOR gains, but it shortened the vestibular time constants in all subjects. This greatly reduced motion sickness produced by OVAR and sensitivity to common transport in the motion susceptible subjects, which persisted for up to 18 weeks. Two motion susceptible subjects who only had aVOR/OKN habituation without being tested with OVAR also became asymptomatic. Normal subjects who were not habituated had no reduction in either their aVOR time constants or motion sickness sensitivity. The opposing aVOR/OKN stimulation, which has not been studied before, was well tolerated, and for the first time was an effective technique for rapid and prolonged habituation of motion sickness without exposure to drugs or other nauseating habituation stimuli. PMID:21287155

There are several mechanisms whereby alteration of barometric pressure can produce vertigo in divers or aviators. Development of a reliable measure of vestibular function in an animal model is the first requirement for further study of these mechanisms. This report presents the development of a rotatory table device capable of evoking the vestibulo-ocular reflex (VOR) of a guinea pig while in a hyperbaric chamber. To assess the reproducibility of this response, eight animals were monitored by electronystagmography during rotations at three table velocities (62.4, 83.3, and 100 degrees/s). Two test sessions were performed on each animal with a 6-hour interval between sessions. The VOR gain was calculated by dividing the average peak velocity of the slow phase component of the nystagmus by the peak stimulus velocity. At least eight observations per test speed were averaged; calibration of eye movement was performed prior to each session by forced ocular abduction. Multifactorial analysis of variance revealed no significant differences (p > .05) between the differing rotation speeds nor between test sessions for individual animals. However, there was a significant difference in VOR gain between animals (p < .002). The VOR gain was then measured, using the same techniques, in another group of seven animals before, during, and after an air dive to the equivalent of 200 feet of seawater (7.06 atmospheres absolute) to assess the effects of nitrogen narcosis. Pre- and post-dive VOR gains were significantly greater than those measured at depth (p < .05). These results are consistent with the slow processing model of nitrogen narcosis and the controversial theory that central nervous system depressants decrease the VOR gain. The results also demonstrate the ability of this inexpensive apparatus to provide a sensitive measure of pressure-induced changes of vestibular function in guinea pigs.

In tadpoles of the Southern Clawed Toad ( Xenopus laevis), the effects of an exposure to hypergravity of several days duration on the development of the roll-induced static vestibuloocular reflex (rVOR) were investigated. Special attention was given to the onset of the 9 or 12 days lasting 3G-period during early life. First recordings of the rVOR characteristics for complete 360 ° rolls of the tadpoles were performed 24 hrs after the end of the 3G-period. The rVOR peak-to-peak amplitudes as well as the VOR-gain for a roll angle of 15 ° from 3G-and 1G-samples recorded at the 2nd and 3rd day after 3G-termination agreed for the youngest group, but were reduced by approx. 30% in the older tadpoles. Long-term observations lasting up to 8 weeks after termination of the 3G-period, demonstrated (i) an early retardation of the development, and (ii) a developmental acceleration in all groups so that after 2 weeks in the stage 6/9- and 33/36-samples and after 8 weeks in the stage 45-tadpoles, the rVOR-amplitude as well as the rVOR-gain for a 15 ° roll were at the same level in both the 3G- and the 1G-samples. The results support the existence of a sensitive period for the rVOR development, and additionally demonstrate the importance of the period of the first appearance of the rVOR for the development of adaptive properties of the underlying neuronal network. They also demonstrate the dominant efficiency of genetic programs in the functional development of the vestibular system. Methodological approaches are discussed which will be useful in the further description of the critical period. They include studies on the neuronogenesis and synaptic maturation within the vestibular pathways as well as on the fundamentals of buoyancy control during swimming. A modular but closed mini-system for experimental use is described which allows survival periods lasting many weeks and multiple types of treatments of developing aquatic animals in orbit, controlled automatically.

In tadpoles of the Southern Clawed Toad (Xenopus laevis), the effects of an exposure to hypergravity of several days duration on the development of the roll-induced static vestibuloocular reflex (rVOR) were investigated. Special attention was given to the onset of the 9 or 12 days lasting 3G-period during early life. First recordings of the rVOR characteristics for complete 360 degrees rolls of the tadpoles were performed 24 hrs after the end of the 3G-period. The rVOR peak-to-peak amplitudes as well as the VOR-gain for a roll angle of 15 degrees from 3G-and 1G-samples recorded at the 2nd and 3rd day after 3G-termination agreed for the youngest group, but were reduced by approx. 30% in the older tadpoles. Long-term observations lasting up to 8 weeks after termination of the 3G-period, demonstrated (i) an early retardation of the development, and (ii) a developmental acceleration in all groups so that after 2 weeks in the stage 6/9- and 33/36-samples and after 8 weeks in the stage 45-tadpoles, the rVOR-amplitude as well as the rVOR-gain for a 15 degrees roll were at the same level in both the 3G- and the 1G-samples. The results support the existence of a sensitive period for the rVOR development, and additionally demonstrate the importance of the period of the first appearance of the rVOR for the development of adaptive properties of the underlying neuronal network. They also demonstrate the dominant efficiency of genetic programs in the functional development of the vestibular system. Methodological approaches are discussed which will be useful in the further description of the critical period. They include studies on the neuronogenesis and synaptic maturation within the vestibular pathways as well as on the fundamentals of buoyancy control during swimming. A modular but closed mini-system for experimental use is described which allows survival periods lasting many weeks and multiple types of treatments of developing aquatic animals in orbit, controlled

1. Two sets of experiments have examined the vestibulo-ocular response (VOR) to repeated sinusoidal rotation (A) in the dark and (B) after attempting visual tracking of a mirror-reversed image of the visual surround.2. In both A and B a horizontal sinusoidal rotational stimulus of 1/6 Hz and 60 degrees /sec angular velocity amplitude was employed, specifically chosen to lie within the presumed range of natural stimulation of the semicircular canals.3. In A each of seven subjects underwent ten 2-min runs of the standard stimulus in the dark on each of three consecutive days, with 3-min rest periods between runs. Using d.c. electro-oculography (EOG) the VOR gain was measured throughout as eye velocity/head velocity. Mental arousal was maintained by competitive mental arithmetic. Constancy of EOG gain was assured by 50 min dark adaptation before experimentation.4. The results of A showed no consistent change of VOR gain over the three times scales of a run, a day and the 3-day experiment.5. In B the same subjects underwent a similar pattern of vestibular stimulation, but during eight of the 2-min daily runs they attempted the reversed visual tracking task. VOR gain was measured during the 1st, 6th and last runs which were conducted in the dark for this purpose. Constancy of EOG gain was maintained by using red light throughout.6. The results of B showed a substantial (approx. 25%) and highly significant (P < 0.001) reduction of VOR gain attributable solely to the 16 min of reversed visual tracking attempted during the 50 min daily experiment. In addition the pre-test control gain was lower on day 3 than on day 1 (approx. 10% attenuation, P < 0.01) indicating a small cumulative effect from beginning to end of the 3-day experiment.7. It is concluded (A) that the repeated vestibular stimulus did not itself cause significant attenuation of VOR gain, but (B) that superposition of a reversed visual tracking task did induce retained VOR attenuation which was solely due to

Downward transport of ozone (O3) from the stratosphere can be a significant contributor to tropospheric O3 background levels. However, this process often is not well represented in current regional models. In this study, we develop a seasonally and spatially varying potential vor...

... omni-directional radio range (VOR) 132° radial. (e) Aircraft navigating in a southeasterly direction... authorized by the Administrator, no person may operate an aircraft in the airspace described in § 93.93.... (b) The aircraft must be equipped as specified in § 91.215(b) of this chapter replying on code...

... omni-directional radio range (VOR) 132° radial. (e) Aircraft navigating in a southeasterly direction... authorized by the Administrator, no person may operate an aircraft in the airspace described in § 93.93.... (b) The aircraft must be equipped as specified in § 91.215(b) of this chapter replying on code...

... omni-directional radio range (VOR) 132° radial. (e) Aircraft navigating in a southeasterly direction... authorized by the Administrator, no person may operate an aircraft in the airspace described in § 93.93.... (b) The aircraft must be equipped as specified in § 91.215(b) of this chapter replying on code...

... VOR Omnidirectional Range Tactical Air Navigation (VORTAC) has made reconfiguration necessary for the safety and management of aircraft operations at the airport. DATES: Effective date, 0901 UTC, May 2, 2013... language in the regulatory text. This action enhances the safety and management of aircraft...

... omni-directional radio range (VOR) 132° radial. (e) Aircraft navigating in a southeasterly direction... authorized by the Administrator, no person may operate an aircraft in the airspace described in § 93.93.... (b) The aircraft must be equipped as specified in § 91.215(b) of this chapter replying on code...

Patients with bilateral vestibular loss experience dehabilitating visual, perceptual, and postural difficulties, and an implantable vestibular prosthesis that could improve these symptoms would be of great benefit to these patients. In previous work, we have shown that a one-dimensional, unilateral canal prosthesis can improve the vestibulooccular reflex (VOR) in canal-plugged squirrel monkeys. In addition to the VOR, the potential effects of a vestibular prosthesis on more complex, highly integrative behaviors, such as the perception of head orientation and posture have remained unclear. We tested a one-dimensional, unilateral prosthesis in a rhesus monkey with bilateral vestibular loss and found that chronic electrical stimulation partially restored the compensatory VOR and also that percepts of head orientation relative to gravity were improved. However, the one-dimensional prosthetic stimulation had no clear effect on postural stability during quiet stance, but sway evoked by head-turns was modestly reduced. These results suggest that not only can the implementation of a vestibular prosthesis provide partial restitution of VOR but may also improve perception and posture in the presence of bilateral vestibular hypofunction (BVH). In this review, we provide an overview of our previous and current work directed towards the eventual clinical implementation of an implantable vestibular prosthesis.

The vestibulo-ocular reflex (VOR) plays an important role in our daily activities by enabling us to fixate on objects during head movements. Modeling and identification of the VOR improves our insight into the system behavior and improves diagnosis of various disorders. However, the switching nature of eye movements (nystagmus), including the VOR, makes dynamic analysis challenging. The first step in such analysis is to segment data into its subsystem responses (here slow and fast segment intervals). Misclassification of segments results in biased analysis of the system of interest. Here, we develop a novel three-step algorithm to classify the VOR data into slow and fast intervals automatically. The proposed algorithm is initialized using a K-means clustering method. The initial classification is then refined using system identification approaches and prediction error statistics. The performance of the algorithm is evaluated on simulated and experimental data. It is shown that the new algorithm performance is much improved over the previous methods, in terms of higher specificity.

...This action proposes to establish two RNAV routes; modify three RNAV routes; and remove one RNAV route in the Charlotte, NC, area. The route changes are proposed to support the Charlotte Optimization of Airspace and Procedures in a Metroplex (OAPM) project. The proposed routes, in combination with existing VOR Federal airways, would provide additional routing options through and around the......

... with our international partners on global strategies for multi-constellation/ multi-frequency GNSS.... RNAV and RNP capabilities will primarily be enabled by the Global Positioning System (GPS) and the Wide... strategy as outlined in the FRN. The FAA is developing an initial VOR MON Plan, which will be...

... within a 5-mile radius of Burlington International Airport, and within 2.4 miles each side of the Burlington VOR/DME 201 radial extending from the 5-mile radius of the airport to 7 miles southwest of the... extending from the 5-mile radius of the airport to 5.4 miles northwest of the airport, and within 4...

Cerebellar climbing fiber activity encodes performance errors during many motor learning tasks, but the role of these error signals in learning has been controversial. We compared two motor learning paradigms that elicited equally robust putative error signals in the same climbing fibers: learned increases and decreases in the gain of the vestibulo-ocular reflex (VOR). During VOR-increase training, climbing fiber activity on one trial predicted changes in cerebellar output on the next trial, and optogenetic activation of climbing fibers to mimic their encoding of performance errors was sufficient to implant a motor memory. In contrast, during VOR-decrease training, there was no trial-by-trial correlation between climbing fiber activity and changes in cerebellar output, and climbing fiber activation did not induce VOR-decrease learning. Our data suggest that the ability of climbing fibers to induce plasticity can be dynamically gated in vivo, even under conditions where climbing fibers are robustly activated by performance errors. DOI: http://dx.doi.org/10.7554/eLife.02076.001 PMID:24755290

A closed circuit flight test was conducted using VORs and NDBs as reference points. The Loran-C data collected during the flight was then compared against a reference provided by a discrete address beacon system facility. Information on the equipment configuration in the aircraft, the flight procedure, and the results obtained are presented.

... airports that have multiple instrument approach procedures. The FAA proposes specific criteria to guide the... outlined below. This Notice is not a part of the FAA's VOR minimum operating network (MON) initiative... multiple IAPs are available. Results of the Flight Safety Foundation study were published in the...

We studied the three-dimensional vestibulo-ocular reflex (VOR) of rhesus monkeys before and after the COSMOS Biosatellite 2229 Mission of 1992-1993. This included tests of ocular counter-rolling (OCR), the gain of the vestibulo-ocular reflex (VOR), and spatial orientation of velocity storage. A four-axis vestibular and oculomotor stimulator was transported to the Institute of Biomedical Problems in Moscow for the pre- and postflight ground-based testing. Twelve normal juvenile male rhesus monkey were implanted surgically with eye coils and tested 60-90 days before spaceflight. Two monkey (7906 and 6151), selected from the twelve as flight animals, flew from 12/29/92 to 1/10/93. Upon recovery, they were tested for 11 days postflight along with three control animals. Compensatory ocular torsion was produced in two ways: (1) Lateral head tilts evoked OCR through otolith-ocular reflexes. OCR was also measured dynamically during off-vertical axis rotation (OVAR). (2) Rotation about a naso-occipital axis that was either vertical of horizontal elicited torsional nystagmus through semicircular canal-ocular reflexes (roll VOR). OCR from the otoliths was substantially reduced (70 percent) for 11 days after reentry on both modes of testing. The gain of the roll VOR was also decreased, but less than OCR. These data demonstrate that there was a long-lasting depression of torsional or roll eye movements after adaptation to microgravity in these monkeys, especially those movements produced by the otolith organs.

... Tactical Air Navigation Aid (VORTAC), and the ASUTA intersection on the United States/Mexican border. The.../Mexican Border and the Julian, CA, 107 (M)/122 (T) radial via Julian; Paradise, CA; INT Paradise 290 and... notified by the Mexican Government that the Penasco VOR in Mexico had been relocated. This proposed...

During sustained constant velocity and low-frequency off-vertical axis rotations (OVAR), otolith signals contribute significantly to slow-phase eye velocity. The adaptive plasticity of these responses was investigated here after semicircular canal plugging. Inactivation of semicircular canals results in a highly compromised and deficient vestibulo-ocular reflex (VOR). Based on the VOR enhancement hypothesis, one could expect an adaptive increase of otolith-borne angular velocity signals due to combined otolith/canal inputs after inactivation of the semicircular canals. Contrary to expectations, however, the steady-state slow-phase velocity during constant velocity OVAR decreased in amplitude over time. A similar progressive decrease in VOR gain was also observed during low-frequency off-vertical axis oscillations. This response deterioration was present in animals with either lateral or vertical semicircular canals inactivated and was limited to the plane(s) of the plugged canals. The results are consistent with the idea that the low-frequency otolith signals do not simply enhance VOR responses. Rather, the nervous system appears to correlate vestibular sensory information from the otoliths and the semicircular canals to generate an integral response to head motion.

...) The VOR must perform in accordance with the “International Standards and Recommended Practices, Aeronautical Telecommunications,” Part I, paragraph 3.3 (Annex 10 to the Convention on International Civil...-service test evaluation period, for calibration and stability The tests are made with a...

...) The VOR must perform in accordance with the “International Standards and Recommended Practices, Aeronautical Telecommunications,” Part I, paragraph 3.3 (Annex 10 to the Convention on International Civil...-service test evaluation period, for calibration and stability The tests are made with a...

...) The VOR must perform in accordance with the “International Standards and Recommended Practices, Aeronautical Telecommunications,” Part I, paragraph 3.3 (Annex 10 to the Convention on International Civil...-service test evaluation period, for calibration and stability The tests are made with a...

Motor learning in the vestibulo-ocular reflex (VOR) and eyeblink conditioning use similar neural circuitry, and they may use similar cellular plasticity mechanisms. Classically conditioned eyeblink responses undergo extinction after prolonged exposure to the conditioned stimulus in the absence of the unconditioned stimulus. We investigated the…

Motor learning is a very basic, essential form of learning that appears to share common mechanisms across different motor systems. We evaluate and compare a few conceptual models for learning in a relatively simple neural system, the vestibulo-ocular reflex (VOR) of vertebrates. We also compare the different animal models that have been used to…

The translational Vestibulo-Ocular Reflex (tVOR) is an important otolith-mediated response to stabilize gaze during natural locomotion. One goal of this study was to develop a measure of the tVOR using a simple hand-operated chair that provided passive vertical motion. Binocular eye movements were recorded with a tight-fitting video mask in ten healthy subjects. Vertical motion was provided by a modified spring-powered chair (swopper.com) at approximately 2 Hz (+/- 2 cm displacement) to approximate the head motion during walking. Linear acceleration was measured with wireless inertial sensors (Xsens) mounted on the head and torso. Eye movements were recorded while subjects viewed near (0.5m) and far (approximately 4m) targets, and then imagined these targets in darkness. Subjects also provided perceptual estimates of target distances. Consistent with the kinematic properties shown in previous studies, the tVOR gain was greater with near targets, and greater with vision than in darkness. We conclude that this portable chair system can provide a field measure of otolith-ocular function at frequencies sufficient to elicit a robust tVOR.

The developments are discussed in the design of a liquid-crystal, visual display, air navigation aid, which uses two VOR signals to locate the aircraft. The system concepts, liquid crystal materials, stability tests, and the electronic system are described. It is concluded that a navigational aid of this type is technically feasible, but not at the projected low cost.

... lateral boundaries using DME from a central VOR (SEA) should be used to define the new Class B boundaries instead of using latitude/longitude fixes to allow DME-equipped aircraft to find the boundary more easily... the proposed 5,000 feet mean sea level (MSL) to 6,000 feet MSL, revising the northeast corner of...

We have completed two studies during the grant period, with manuscripts published or ready for submission for publication: (1) Dual adaptation and adaptive generalization in the human vestibuloocular reflex and (2) Frequency vs. acceleration specificity in human VOR adaptation. In the 1st study two studies examined the possibility that rotational VOR plasticity is subject to dual adaptation and adaptive generalization. Subjects in the experimental condition were exposed to an altered visual-vestibular environment for about four minutes every day for five consecutive days. The working hours between these testing sessions constituted re-exposure to the normal visual environment. Thus, subjects were repeatedly adapting and re-adapting to both environments which is a condition designed to produce dual adaptation. In each training session a measure of baseline VOR gain was obtained (in the dark). A small laser spot (the only visual stimulus) was systematically moved in the same direction as the subject's head, but by half the angle of rotation (target/head gain = 0.5). This resulted in adaptation values relativized to the non-adapted gain of each subject. These values were then analyzed using an analysis of variance with day and session (within a day) as factors. In the 2nd study human VOR adaption has been assumed to be frequency specific, despite the fact that the semicircular canals are simulated by rotational acceleration and not frequency per se.

... Route J-2, and VOR Federal airways V-16, V-66, and V-202 in southern Arizona and New Mexico. The FAA is... V-16, V-66, and V-202. This action is necessary due to the decommissioning of the Cochise, AZ... remainder of the route would be unchanged). The portion of V-16 that currently extends from Tucson, AZ;...

This study aims to evaluate the effect of efflux pump modulators (EPMs) on the minimal inhibitory concentration (MIC) of fluconazole (FLZ) and voriconazole (VOR) in Malassezia furfur and Malassezia pachydermatis. The in vitro efficacy of azoles, in combination with EPMs (ie haloperidol-HAL, promethazine-PTZ and cyclosporine A-CYS), against 21 M. furfur from bloodstream infection patients and 14 M. pachydermatis from the skin of dogs with dermatitis, was assessed using a broth microdilution chequerboard analysis. Data were analysed using the model-fractional inhibitory concentration index (FICI) method. The MIC of FLZ and VOR of Malassezia spp. decreased in the presence of sub-inhibitory concentrations of HAL and/or PTZ. The synergic effect was observed only in strains with FLZ MIC≥128 μg/mL for M. furfur, FLZ MIC≥64 μg/mL for M. pachydermatis and VOR MIC≥4 μg/mL in both Malassezia spp. These results suggest that the drug efflux pumps are involved as defence mechanisms to azole drugs in Malassezia yeast. The synergism might be related to an increased expression of efflux pump genes, eventually resulting in azole resistance phenomena. Finally, the above FLZ and VOR MIC values might be considered the cut-off to discriminate susceptible and resistant strains.

Although intact vestibular function is essential in maintaining spatial orientation, no good screening tests of vestibular function are available to the aviation community. High frequency voluntary head rotation was selected as a vestibular stimulus to isolate the vestibulo-ocular reflex (VOR) from visual influence. A dynamic visual acuity test that incorporates voluntary head rotation was evaluated as a potential vestibular function screening tool. Twenty-seven normal subjects performed voluntary sinusoidal head rotation at frequencies from 0.7-4.0 Hz under three different visual conditions: visually-enhanced VOR, normal VOR, and visually suppressed VOR. Standardized Baily-Lovie chart letters were presented on a computer monitor in front of the subject, who then was asked to read the letters while rotating his head horizontally. The electro-oculogram and dynamic visual acuity score were recorded and analyzed. There were no significant differences in gain or phase shift among three visual conditions in the frequency range of 2.8 to 4.0 Hz. The dynamic visual acuity score shifted less than 0.3 logMAR at frequencies under 2.0 Hz. The dynamic visual acuity test at frequencies a round 2.0 Hz can be recommended for evaluating vestibular function.

The vestibulo-ocular reflex (VOR) may be altered by weightlessness. Since this reflex plays a large role in visual stabilization, it was important to document any changes caused by space flight. This is a report on findings on STS-4 through 6 and is part of a larger study of neurosensory adaptation done on STS-4 through 8. Voluntary horizontal head oscillations at 1/3 Hz with amplitude of 30 deg right and left of center were recorded by a potentiometer and compared to eye position recorded by electroculography under the following conditions: eyes open, head fixed, tracking horizontal targets switched 0, 15, and 30 degrees right and left (optokinetic reflex - OKR - and calibration); eyes open and fixed on static external target with oscillation, (vestibulo ocular reflex, eyes closed - VOR EC); eyes open and wearing opaque goggles with target fixed in imagination (vestibulo-ocular reflex, eyes shaded - VOR ES); and eyes open and fixed on a head synchronized target with head oscillation (VOR suppression). No significant changes were found in voluntary head oscillation frequency or amplitude in those with (n=5), and without (n=3), space motion sickness (SMS), with phase of flight or test condition. Variations in head oscillation were too small to have produced detectable changes in test results.

Global Positioning System ( GPS ) and the Long Range Navigation System LORAN-C. The...in these developments are new satellite technologies such as the NAVSTAR Global Positioning System ( GPS ) and improvements of existing systems such as...Omnidirectional Range (VOR) stations, the Global Positioning System ( GPS ) satellites, and stars (celestial fixes). A vehicle can obtain range (p) or bearing

The vestibulo-ocular reflexes (VOR) are determined not only by angular acceleration, but also by the presence of gravity and linear acceleration. This phenomenon was studied by measuring three-dimensional nystagmic eye movements, with implanted search coils, in six male squirrel monkeys during eccentric rotation. Monkeys were rotated in the dark at a constant velocity of 200 degrees/s (centrally or 79 cm off axis) with the axis of rotation always aligned with gravity and the spinal axis of the upright monkeys. The monkey's orientation (facing-motion or back-to-motion) had a dramatic influence on the VOR. These experiments show that: (a) the axis of eye rotation always shifted toward alignment with gravito-inertial force; (b) the peak value of horizontal slow phase eye velocity was greater with the monkey facing-motion than with back-to-motion; and (c) the time constant of horizontal eye movement decay was smaller with the monkey facing-motion than with back-to-motion. All of these findings were statistically significant and consistent across monkeys. In another set of tests, the same monkeys were rapidly tilted about their naso-occipital (roll) axis. Tilted orientations of 45 degrees and 90 degrees were maintained for 1 min. Other than a compensatory angular VOR during the angular rotation, no consistent eye velocity response was observed during or following the tilt for any of the six monkeys. The absence of any eye movement response following tilt weighs against the possibility that translational linear VOR responses are due to simple high-pass filtering of the otolith signals. The VOR response during eccentric rotation was divided into the more familiar angular VOR and linear VOR components. The angular component is known to depend upon semicircular canal dynamics and central influences. The linear component of the response decays rapidly with a mean duration of only 6.6 s, while the axis of eye rotation rapidly aligns (< 10 s) with gravito-inertial force. These

During early periods of life, modifications of the gravitational environment affect the development of sensory, neuronal and motor systems. The vestibular system exerts significant effects on motor networks that control eye and body posture as well as swimming. The objective of the present study was to study whether altered gravity (AG) affects vestibuloocular and spinal motor systems in a correlated manner. During the French Soyuz taxi flight Andromède to the International Space Station ISS (launch: October 21, 2001; landing: October 31, 2001) Xenopus laevis embryos were exposed for 10 days to microgravity (microg). In addition, a similar experiment with 3g-hypergravity (3g) was performed in the laboratory. At onset of AG, embryos had reached developmental stages 24 to 27. After exposure to AG, each tadpole was tested for its roll-induced vestibuloocular reflex (rVOR) and 3 hours later it was tested for the neuronal activity recorded from the ventral roots (VR) during fictive swimming. During the post-AG recording periods tadpoles had reached developmental stages 45 to 47. It was observed that microgravity affected VR activity during fictive swimming and rVOR. In particular, VR activity changes included a significant decrease of the rostrocaudal delay and a significant increase of episode duration. The rVOR-amplitude was transiently depressed. Hypergravity was less effective on the locomotor pattern; occurring effects on fictive swimming were the opposite of microg effects. As after microgravity, the rVOR was depressed after 3g-exposure. All modifications of the rVOR and VR-activity recovered to normal levels within 4 to 7 days after termination of AG. Significant correlations between the rVOR amplitude and VR activity of respective tadpoles during the recording period have been observed in both tadpoles with or without AG experience. The data are consistent with the assumptions that during this period of life which is characterized by a progressive development

Sensory systems often provide ambiguous information. Integration of various sensory cues is required for the CNS to resolve sensory ambiguity and elicit appropriate responses. The vestibular system includes two types of sensors: the semicircular canals, which measure head rotation, and the otolith organs, which measure gravito-inertial force (GIF), the sum of gravitational force and inertial force due to linear acceleration. According to Einstein's equivalence principle, gravitational force is indistinguishable from inertial force due to linear acceleration. As a consequence, otolith measurements must be supplemented with other sensory information for the CNS to distinguish tilt from translation. The GIF resolution hypothesis states that the CNS estimates gravity and linear acceleration, so that the difference between estimates of gravity and linear acceleration matches the measured GIF. Both otolith and semicircular canal cues influence this estimation of gravity and linear acceleration. The GIF resolution hypothesis predicts that inaccurate estimates of both gravity and linear acceleration can occur due to central interactions of sensory cues. The existence of specific patterns of vestibuloocular reflexes (VOR) related to these inaccurate estimates can be used to test the GIF resolution hypothesis. To investigate this hypothesis, we measured eye movements during two different protocols. In one experiment, eight subjects were rotated at a constant velocity about an earth-vertical axis and then tilted 90 degrees in darkness to one of eight different evenly spaced final orientations, a so-called "dumping" protocol. Three speeds (200, 100, and 50 degrees /s) and two directions, clockwise (CW) and counterclockwise (CCW), of rotation were tested. In another experiment, four subjects were rotated at a constant velocity (200 degrees /s, CW and CCW) about an earth-horizontal axis and stopped in two different final orientations (nose-up and nose-down), a so

We previously reported that inhibition of autophagy significantly augmented the anticancer activity of the histone deacetylase (HDAC) inhibitor vorinostat (VOR) through a cathepsin D-mediated mechanism. We thus conducted a first-in-human study to investigate the safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the combination of the autophagy inhibitor hydroxychloroquine (HCQ) and VOR in patients with advanced solid tumors. Of 27 patients treated in the study, 24 were considered fully evaluable for study assessments and toxicity. Patients were treated orally with escalating doses of HCQ daily (QD) (d 2 to 21 of a 21-d cycle) in combination with 400 mg VOR QD (d one to 21). Treatment-related adverse events (AE) included grade 1 to 2 nausea, diarrhea, fatigue, weight loss, anemia, and elevated creatinine. Grade 3 fatigue and/or myelosuppression were observed in a minority of patients. Fatigue and gastrointestinal AE were dose-limiting toxicities. Six-hundred milligrams HCQ and 400 mg VOR was established as the maximum tolerated dose and recommended phase II regimen. One patient with renal cell carcinoma had a confirmed durable partial response and 2 patients with colorectal cancer had prolonged stable disease. The addition of HCQ did not significantly impact the PK profile of VOR. Treatment-related increases in the expression of CDKN1A and CTSD were more pronounced in tumor biopsies than peripheral blood mononuclear cells. Based on the safety and preliminary efficacy of this combination, additional clinical studies are currently being planned to further investigate autophagy inhibition as a new approach to increase the efficacy of HDAC inhibitors.

Purpose Listing’s law (LL) constrains the rotational axes of saccades and pursuit eye movements to Listing’s plane (LP). In the velocity domain, LL is ordinarily equivalent to a tilt in the ocular velocity axis equal to half the change in eye position, giving a tilt angle ratio (TAR) of 0.5. This study was undertaken to investigate vertical saccade behavior after the yaw vestibulo-ocular reflex (VOR) had driven eye torsion out of LP, an initial condition causing the position and velocity domain formulations of LL to differ. Methods Binocular eye and head motions were recorded with magnetic search coils in eight humans. With the head immobile, LP was determined for each eye, and mean TAR was 0.50 ± 0.07 (mean ± SD) for horizontal and 0.45 ± 0.11 for vertical saccades. The VOR was evoked by transient, whole-body yaw at 2800 deg/s2 peak acceleration, capable of evoking large, uninterrupted VOR slow phases. Before rotation, subjects viewed a target at eye level, 20° up, or 20° down. In two thirds of the trials, the target moved upward or downward at systematically varying times, triggering a vertical saccade during the horizontal VOR slow phase. Results Because the head rotation axis was generally misaligned with LP, the eye averaged 3.6° out of LP at vertical saccade onset. During the saccade, eye position continued to depart LP by an average 0.8°. The horizontal TAR at saccade onset was 0.29 ± 0.07. At peak saccade velocity 35 ± 3 ms later, the vertical TAR was 0.45 ± 0.07, statistically similar to that of head fixed saccades. Saccades did not return to LP. Conclusions Although they did not observe the position domain formulation of LL, vertical saccades, during the VOR, observed the half-angle velocity domain formulation of LL. PMID:16043853

The aim of this study was to test the effects of a sustained nystagmus on the head impulse response of the vestibulo-ocular reflex (VOR) in healthy subjects. VOR gain (slow-phase eye velocity/head velocity) was measured using video head impulse test goggles. Acting as a surrogate for a spontaneous nystagmus (SN), a post-rotatory nystagmus (PRN) was elicited after a sustained, constant-velocity rotation, and then head impulses were applied. 'Raw' VOR gain, uncorrected for PRN, in healthy subjects in response to head impulses with peak velocities in the range of 150°/s-250°/s was significantly increased (as reflected in an increase in the slope of the gain versus head velocity relationship) after inducing PRN with slow phases of nystagmus of high intensity (>30°/s) in the same but not in the opposite direction as the slow-phase response induced by the head impulses. The values of VOR gain themselves, however, remained in the normal range with slow-phase velocities of PRN < 30°/s. Finally, quick phases of PRN were suppressed during the first 20-160 ms of a head impulse; the time frame of suppression depended on the direction of PRN but not on the duration of the head impulse. Our results in normal subjects suggest that VOR gains measured using head impulses may have to be corrected for any superimposed SN when the slow-phase velocity of nystagmus is relatively high and the peak velocity of the head movements is relatively low. The suppression of quick phases during head impulses may help to improve steady fixation during rapid head movements.

The present study investigated the simultaneous oxidation of pyruvate and amino acids during H2-evolving growth of the hyperthermophilic archaeon Thermococcus kodakarensis. The comparison of mass balance between a cytosolic hydrogenase (HYH)-deficient strain (the ΔhyhBGSL strain) and the parent strain indicated that NADPH generated via H2 uptake by HYH was consumed by reductive amination of 2-oxoglutarate catalyzed by glutamate dehydrogenase. Further examinations were done to elucidate functions of three enzymes potentially involved in pyruvate oxidation: pyruvate formate-lyase (PFL), pyruvate:ferredoxin oxidoreductase (POR), and 2-oxoisovalerate:ferredoxin oxidoreductase (VOR) under the HYH-deficient background in T. kodakarensis. No significant change was observed by deletion of pflDA, suggesting that PFL had no critical role in pyruvate oxidation. The growth properties and mass balances of ΔporDAB and ΔvorDAB strains indicated that POR and VOR specifically functioned in oxidation of pyruvate and branched-chain amino acids, respectively, and the lack of POR or VOR was compensated for by promoting the oxidation of another substrate driven by the remaining oxidoreductase. The H2 yields from the consumed pyruvate and amino acids were increased from 31% by the parent strain to 67% and 82% by the deletion of hyhBGSL and double deletion of hyhBGSL and vorDAB, respectively. Significant discrepancies in the mass balances were observed in excess formation of acetate and NH3, suggesting the presence of unknown metabolisms in T. kodakarensis grown in the rich medium containing pyruvate.

We investigated the dynamic properties of the human vestibulo-ocular reflex (VOR) during roll head rotations in three human subjects using the magnetic search coil technique. In the first of two experiments, we quantify the behavior of the ocular motor plant in the torsional plane. The subject's eye was mechanically displaced into intorsion, extorsion or abduction, and the dynamic course of return of the eye to its resting position was measured. The mean predominant time constants of return were 210 msec from intorsion, 83 msec from extorsion, and 217 msec from abduction, although there was considerable variability of results from different trials and subjects. In the second experiment, we quantify the efficacy of velocity-to-position integration of the vestibular signal. Position-step stimuli were used to test the torsional or horizontal VOR, being applied with subjects heads erect or supine. After a torsional position-step, the eye drifted back to its resting position, but after a horizontal position-step the eye held its new horizontal position. To interpret these responses we used a simple model of the VOR with parameters of the ocular motor plant set to values determined during Exp 1. The time constant of the velocity-to-position neural integrator was smaller (typically 2 sec) in the torsional plane than in the horizontal plane (> 20 sec). No disconjugacy of torsional eye movements was observed. Thus, the dynamic properties of the VOR in roll differ significantly from those of the VOR in yaw, reflecting different visual demands placed on this reflex in these two planes.

The translational vestibulo-ocular reflex (tVOR) is an otolith-mediated response that stabilizes near vision during linear acceleration at higher frequencies where visually mediated reflexes are not adequate. The modulation of horizontal and vergence eye movements during Off-Vertical Axis Rotation (OVAR) are presumed to reflect the tVOR in response to the continuously varying linear acceleration in the interaural and nasooccipital axes, respectively. The purpose of this study was to examine the effect of frequency and fixation distance on the modulation of slow phase eye velocity (SPV) as further evidence that the tVOR is elicited during OVAR. Eighteen subjects were rotated about their longitudinal axis tilted by 30 deg off-vertical. Rotational velocities varied between 18 and 288 deg/sec corresponding to a frequency range of 0.05 to 0.8 Hz. Fixation distance was altered by asking subjects to imagine stationary targets that were briefly presented at 0.5, 1 and 2 m during some rotation cycles. The target flash was 40 msec in the nose-up position at eye level. Oculomotor responses were recorded in the dark using infrared binocular videography. Sinusoidal curve fits were used to derive amplitude, phase and bias velocity of the eye movements across multiple rotation cycles. Consistent with previous studies, the modulation of both horizontal and vergence SPV increased with stimulus frequency. The effect of fixation distance was negligible at lower frequencies. The modulation of horizontal and vergence SPV was; however, proportional to fixation distance during OVAR at 0.8 Hz. This increasing sensitivity and dependence on fixation distance of horizontal and vergence SPV during OVAR is consistent with tVOR characteristics measured during other types of linear motion. We conclude that the modulation of horizontal and vergence SPV will be diagnostically more useful at higher stimulus frequencies where the tVOR is more robust.

We characterized the interaural translational vestibulo-ocular reflex (tVOR) in 6 normal humans to brief (approximately 200 ms), high-acceleration (0.4-1.4g) stimuli, while they fixed targets at 15 or 30 cm. The latency was 19 +/- 5 ms at 15-cm and 20 +/- 12 ms at 30-cm viewing. The gain was quantified using the ratio of actual to ideal behavior. The median position gain (at time of peak head velocity) was 0.38 and 0.37, and the median velocity gain, 0.52 and 0.62, at 15- and 30-cm viewing, respectively. These results suggest the tVOR scales proportionally at these viewing distances. Likewise, at both viewing distances, peak eye velocity scaled linearly with peak head velocity and gain was independent of peak head acceleration. A saccade commonly occurred in the compensatory direction, with a greater latency (165 vs. 145 ms) and lesser amplitude (1.8 vs. 3.2 deg) at 30- than 15-cm viewing. Even with saccades, the overall gain at the end of head movement was still considerably undercompensatory (medians 0.68 and 0.77 at 15- and 30-cm viewing). Monocular viewing was also assessed at 15-cm viewing. In 4 of 6 subjects, gains were the same as during binocular viewing and scaled closely with vergence angle. In sum the low tVOR gain and scaling of the response with viewing distance and head velocity extend previous results to higher acceleration stimuli. tVOR latency (approximately 20 ms) was lower than previously reported. Saccades are an integral part of the tVOR, and also scale with viewing distance.

We characterized the interaural translational vestibulo-ocular reflex (tVOR) in 6 normal humans to brief (approximately 200 ms), high-acceleration (0.4-1.4g) stimuli, while they fixed targets at 15 or 30 cm. The latency was 19 +/- 5 ms at 15-cm and 20 +/- 12 ms at 30-cm viewing. The gain was quantified using the ratio of actual to ideal behavior. The median position gain (at time of peak head velocity) was 0.38 and 0.37, and the median velocity gain, 0.52 and 0.62, at 15- and 30-cm viewing, respectively. These results suggest the tVOR scales proportionally at these viewing distances. Likewise, at both viewing distances, peak eye velocity scaled linearly with peak head velocity and gain was independent of peak head acceleration. A saccade commonly occurred in the compensatory direction, with a greater latency (165 vs. 145 ms) and lesser amplitude (1.8 vs. 3.2 deg) at 30- than 15-cm viewing. Even with saccades, the overall gain at the end of head movement was still considerably undercompensatory (medians 0.68 and 0.77 at 15- and 30-cm viewing). Monocular viewing was also assessed at 15-cm viewing. In 4 of 6 subjects, gains were the same as during binocular viewing and scaled closely with vergence angle. In sum the low tVOR gain and scaling of the response with viewing distance and head velocity extend previous results to higher acceleration stimuli. tVOR latency (approximately 20 ms) was lower than previously reported. Saccades are an integral part of the tVOR, and also scale with viewing distance.

1. These experiments investigated plastic changes in the vestibulo-ocular reflex (VOR) of human subjects consequent to long-term optical reversal of vision during free head movement. Horizontal vision-reversal was produced by head-mounted dove prisms. Four normal adults were continuously exposed to these conditions during 2, 6, 7 and 27 days respectively.2. A sinusoidal rotational stimulus, previously shown to be nonhabituating (1/6 Hz; 60 degrees /sec amplitude), was used to test the VOR in the dark at frequent intervals both during the period of vision-reversal and an equal period after return to normal vision. D.c. electro-oculography (EOG) was used to record eye movement, taking care to avoid changes of EOG gain due to light/dark adaptation of the retina.3. All subjects showed substantial reduction of VOR gain (eye velocity/head velocity) during the first 2 days of vision-reversal. The 6-, 7- and 27-day subjects showed further reduction of gain which reached a low plateau at about 25% the normal value by the end of one week. At this time the attenuation of some EOG records was so marked as to defy extraction of a meaningful sinusoidal signal.4. After removal of the prisms VOR gain recovered along a time course which approximated that of the original adaptive attenuation.5. In the 27-day experiment large changes of phase developed in the VOR during the second week of vision-reversal. These changes generally progressed in a lagging sense, to reach 130 degrees phase lag relative to normal by the beginning of the third week. Accompanying this was a considerable restoration of gain from 25 to 50% the normal value. These adapted conditions, which approximate functional reversal of the reflex, were then maintained steady, even overnight, until return to normal vision on the 28th day.6. Thereafter, whereas VOR phase returned to near-normal in 2 hr, restoration of gain occupied a further 2-3 weeks.7. There was a highly systematic relation between instantaneous gain and

Vertical head and eye coordination was studied as a function of viewing distance during locomotion. Vertical head translation and pitch movements were measured using a video motion analysis system (Optotrak 3020). Vertical eye movements were recorded using a video-based pupil tracker (Iscan). Subjects (five) walked on a linear treadmill at a speed of 1.67 m/s (6 km/h) while viewing a target screen placed at distances ranging from 0.25 to 2.0 m at 0. 25-m intervals. The predominant frequency of vertical head movement was 2 Hz. In accordance with previous studies, there was a small head pitch rotation, which was compensatory for vertical head translation. The magnitude of the vertical head movements and the phase relationship between head translation and pitch were little affected by viewing distance, and tended to orient the naso-occipital axis of the head at a point approximately 1 m in front of the subject (the head fixation distance or HFD). In contrast, eye velocity was significantly affected by viewing distance. When viewing a far (2-m) target, vertical eye velocity was 180 degrees out of phase with head pitch velocity, with a gain of 0. 8. This indicated that the angular vestibulo-ocular reflex (aVOR) was generating the eye movement response. The major finding was that, at a close viewing distance (0.25 m), eye velocity was in phase with head pitch and compensatory for vertical head translation, suggesting that activation of the linear vestibulo-ocular reflex (lVOR) was contributing to the eye movement response. There was also a threefold increase in the magnitude of eye velocity when viewing near targets, which was consistent with the goal of maintaining gaze on target. The required vertical lVOR sensitivity to cancel an unmodified aVOR response and generate the observed eye velocity magnitude for near targets was almost 3 times that previously measured. Supplementary experiments were performed utilizing body-fixed active head pitch rotations at 1 and 2 Hz

The adaptive plasticity of the spatial organization of the vestibuloocular reflex (VOR) has been investigated in intact and canal-plugged primates using 2-h exposure to conflicting visual (optokinetic, OKN) and vestibular rotational stimuli about mutually orthogonal axes (generating torsional VOR + vertical OKN, torsional VOR + horizontal OKN, vertical VOR + horizontal OKN, and horizontal VOR + vertical OKN). Adaptation protocols with 0.5-Hz (+/-18 degrees ) head movements about either an earth-vertical or an earth-horizontal axis induced orthogonal response components as high as 40-70% of those required for ideal adaptation. Orthogonal response gains were highest at the adapting frequency with phase leads present at lower and phase lags present at higher frequencies. Furthermore, the time course of adaptation, as well as orthogonal response dynamics were similar and relatively independent of the particular visual/vestibular stimulus combination. Low-frequency (0. 05 Hz, vestibular stimulus: +/-60 degrees ; optokinetic stimulus: +/-180 degrees ) adaptation protocols with head movements about an earth-vertical axis induced smaller orthogonal response components that did not exceed 20-40% of the head velocity stimulus (i.e., approximately 10% of that required for ideal adaptation). At the same frequency, adaptation with head movements about an earth-horizontal axis generated large orthogonal responses that reached values as high as 100-120% of head velocity after 2 h of adaptation (i.e., approximately 40% of ideal adaptation gains). The particular spatial and temporal response characteristics after low-frequency, earth-horizontal axis adaptation in both intact and canal-plugged animals strongly suggests that the orienting (and perhaps translational) but not inertial (velocity storage) components of the primate otolith-ocular system exhibit spatial adaptability. Due to the particular nested arrangement of the visual and vestibular stimuli, the optic flow pattern

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral labyrinthectomy. Spontaneous nystagmus was measured at the beginning and end of each testing session. During the period that animals were kept in darkness (4 days), the nystagmus at each of these times measured approximately 20 degrees /s. Within 18-24 h after return to the light, the nystagmus (measured in darkness) decreased to 2.8 +/- 1.5 degrees /s (mean +/- SD) when recorded at the beginning but was 20.3 +/- 3.9 degrees /s at the end of the testing session. The latency of the VOR measured from responses to steps of acceleration (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) was 8.4 +/- 0.3 ms for responses to ipsilesional rotations and 7.7 +/- 0.4 ms for contralesional rotations. During the period that animals were kept in darkness after the labyrinthectomy, the gain of the VOR measured during the steps of acceleration was 0.67 +/- 0.12 for contralesional rotations and 0.39 +/- 0.04 for ipsilesional rotations. Within 18-24 h after return to light, the VOR gain for contralesional rotations increased to 0.87 +/- 0.08, whereas there was only a slight increase for ipsilesional rotations to 0.41 +/- 0. 06. A symmetrical increase in the gain measured at the plateau of head velocity was noted after the animals were returned to light. The VOR evoked by sinusoidal rotations of 2-15 Hz, +/-20 degrees /s, showed a better recovery of gain at lower (2-4 Hz) than at higher (6-15 Hz) frequencies. At 0.5 Hz, gain decreased symmetrically when the peak amplitude was increased from 20 to 100 degrees /s. At 10 Hz, gain was decreased for ipsilesional half-cycles and increased for contralesional half-cycles when velocity was raised from 20 to 50 degrees /s. A model incorporating linear and nonlinear pathways was used to simulate the data. Selective increases in the gain for the linear pathway accounted for the

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in five squirrel monkeys with intact vestibular function. The VOR evoked by steps of acceleration in darkness (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) began after a latency of 7.3 +/- 1.5 ms (mean +/- SD). Gain of the reflex during the acceleration was 14.2 +/- 5.2% greater than that measured once the plateau head velocity had been reached. A polynomial regression was used to analyze the trajectory of the responses to steps of acceleration. A better representation of the data was obtained from a polynomial that included a cubic term in contrast to an exclusively linear fit. For sinusoidal rotations of 0.5-15 Hz with a peak velocity of 20 degrees /s, the VOR gain measured 0.83 +/- 0.06 and did not vary across frequencies or animals. The phase of these responses was close to compensatory except at 15 Hz where a lag of 5.0 +/- 0.9 degrees was noted. The VOR gain did not vary with head velocity at 0.5 Hz but increased with velocity for rotations at frequencies of >/=4 Hz (0. 85 +/- 0.04 at 4 Hz, 20 degrees /s; 1.01 +/- 0.05 at 100 degrees /s, P < 0.0001). No responses to these rotations were noted in two animals that had undergone bilateral labyrinthectomy indicating that inertia of the eye had a negligible effect for these stimuli. We developed a mathematical model of VOR dynamics to account for these findings. The inputs to the reflex come from linear and nonlinear pathways. The linear pathway is responsible for the constant gain across frequencies at peak head velocity of 20 degrees /s and also for the phase lag at higher frequencies being less than that expected based on the reflex delay. The frequency- and velocity-dependent nonlinearity in VOR gain is accounted for by the dynamics of the nonlinear pathway. A transfer function that increases the gain of this pathway with frequency and a term related to the third power of head

We have determined a critical period for vestibular development in zebrafish by using a bioreactor designed by NASA to simulate microgravity for cells in culture. A critical period is defined as the briefest period of time during development when stimulus deprivation results in long lasting or permanent sensory deficits. Zebrafish eggs were collected within 3 hours of being laid and fertilized. In experiment 1, eggs were placed in the bioreactor at 3, 24, 30, 36, 48, or 72 hours postfertilization (hPF) and maintained in the bioreactor until 96 hPF. In experiment 2, eggs were placed in the bioreactor immediately after they were collected and maintained in the bioreactor until 24, 36, 48, 60, 66, 72, or 96 hPF. Beginning at 96 hPF, all larvae had their vestibulo-ocular reflexes (VOR) evaluated once each day for 5 days. Only larvae that hatched from eggs that were placed in the bioreactor before 30 hPF in experiment 1 or removed from the bioreactor later than 66 hPF in experiment 2 had VOR deficits that persisted for at least 5 days. These data suggest a critical period for vestibular development in the zebrafish that begins before 30 hPF and ends after 66 hPF. To confirm this, zebrafish eggs were placed in the bioreactor at 24 hPF and removed at 72 hPF. VORs were evaluated in these larvae once each day for 5 days beginning at 96 hPF. These larvae had VOR deficits that persisted for at least 5 days. In addition, larvae that had been maintained in the bioreactor from 24 to 66 hPF or from 30 to 72 hPF, had only temporary VOR deficits. In a final experiment, zebrafish eggs were placed in the bioreactor at 3 hPF and removed at 96 hPF but the bioreactor was turned off from 24 hPF to 72 hPF. These larvae had normal VORs when they were removed from the bioreactor at 96 hPF. Taken as a whole, these data support the idea that there is a critical period for functional maturation of the zebrafish vestibular system. The developmental period identified includes the timeframe

Blasts (explosions) are the most common mechanism of injury in modern warfare. Traumatic brain injury (TBI) and dizziness are common sequelae associated with blasts, and many service members (SMs) report symptoms worsen with activity. The purpose of this study was to measure angular vestibulo-ocular reflex gain (aVOR) of blast-exposed SMs with TBI during head impulse testing. We also assessed their symptoms during exertion. Twenty-four SMs recovering from TBI were prospectively assigned to one of two groups based on the presence or absence of dizziness. Wireless monocular scleral search coil and rate sensor were used to characterize active and passive yaw and pitch head and eye rotations. Visual analog scale (VAS) was used to monitor symptoms during fast walking/running. For active yaw head impulses, aVOR gains were significantly lower in the symptomatic group (0.79 ± 0.15) versus asymptomatic (0.87 ± 0.18), but not for passive head rotation. For pitch head rotation, the symptomatic group had both active (0.915 ± 0.24) and passive (0.878 ± 0.22) aVOR gains lower than the asymptomatic group (active 1.03 ± 0.27, passive 0.97 ± 0.23). Some SMs had elevated aVOR gain. VAS scores for all symptoms were highest during exertion. Our data suggest symptomatic SMs with TBI as a result of blast have varied aVOR gain during high-velocity head impulses and provide compelling evidence of pathology affecting the vestibular system. Potential loci of injury in this population include the following: disruption of pathways relaying vestibular efference signals, differential destruction of type I vestibular hair cells, or selective damage to irregular afferent pathways—any of which may explain the common discrepancy between reports of vestibular-like symptoms and laboratory testing results. significantly reduced pitch aVOR in symptomatic SMs and peak symptom severity during exertional testing support earlier findings in the chronic blast-exposed active duty SMs. PMID:21113582

Nystagmus induced by off-vertical axis rotation (OVAR) about a head yaw axis is composed of a yaw bias velocity and modulations in eye position and velocity as the head changes orientation relative to gravity. The bias velocity is dependent on the tilt of the rotational axis relative to gravity and angular head velocity. For axis tilts <15 degrees, bias velocities increased monotonically with increases in the magnitude of the projected gravity vector onto the horizontal plane of the head. For tilts of 15-90 degrees, bias velocity was independent of tilt angle, increasing linearly as a function of head velocity with gains of 0.7-0.8, up to the saturation level of velocity storage. Asymmetries in OVAR bias velocity and asymmetries in the dominant time constant of the angular vestibuloocular reflex (aVOR) covaried and both were reduced by administration of baclofen, a GABA(B) agonist. Modulations in pitch and roll eye positions were in phase with nose-down and side-down head positions, respectively. Changes in roll eye position were produced mainly by slow movements, whereas vertical eye position changes were characterized by slow eye movements and saccades. Oscillations in vertical and roll eye velocities led their respective position changes by approximately 90 degrees, close to an ideal differentiation, suggesting that these modulations were due to activation of the orienting component of the linear vestibuloocular reflex (lVOR). The beating field of the horizontal nystagmus shifted the eyes 6.3 degrees /g toward gravity in side down position, similar to the deviations observed during static roll tilt (7.0 degrees /g). This demonstrates that the eyes also orient to gravity in yaw. Phases of horizontal eye velocity clustered ~180 degrees relative to the modulation in beating field and were not simply differentiations of changes in eye position. Contributions of orientating and compensatory components of the lVOR to the modulation of eye position and velocity were

Blasts (explosions) are the most common mechanism of injury in modern warfare. Traumatic brain injury (TBI) and dizziness are common sequelae associated with blasts, and many service members (SMs) report symptoms worsen with activity. The purpose of this study was to measure angular vestibulo-ocular reflex gain (aVOR) of blast-exposed SMs with TBI during head impulse testing. We also assessed their symptoms during exertion. Twenty-four SMs recovering from TBI were prospectively assigned to one of two groups based on the presence or absence of dizziness. Wireless monocular scleral search coil and rate sensor were used to characterize active and passive yaw and pitch head and eye rotations. Visual analog scale (VAS) was used to monitor symptoms during fast walking/running. For active yaw head impulses, aVOR gains were significantly lower in the symptomatic group (0.79 ± 0.15) versus asymptomatic (0.87 ± 0.18), but not for passive head rotation. For pitch head rotation, the symptomatic group had both active (0.915 ± 0.24) and passive (0.878 ± 0.22) aVOR gains lower than the asymptomatic group (active 1.03 ± 0.27, passive 0.97 ± 0.23). Some SMs had elevated aVOR gain. VAS scores for all symptoms were highest during exertion. Our data suggest symptomatic SMs with TBI as a result of blast have varied aVOR gain during high-velocity head impulses and provide compelling evidence of pathology affecting the vestibular system. Potential loci of injury in this population include the following: disruption of pathways relaying vestibular efference signals, differential destruction of type I vestibular hair cells, or selective damage to irregular afferent pathways-any of which may explain the common discrepancy between reports of vestibular-like symptoms and laboratory testing results. Significantly reduced pitch aVOR in symptomatic SMs and peak symptom severity during exertional testing support earlier findings in the chronic blast-exposed active duty SMs.

The performance of navigation systems is always reduced by unwanted multipath propagation. This is especially of practical importance for airborne navigation systems like the instrument landing system (ILS) or the VHF omni directional radio range (VOR). Nevertheless, the quantitative analysis of corresponding, potentially harmful multipath propagation disturbances is very difficult due to the large parameter space. Experimentally difficulties arise due to very expensive, real scale measurement campaigns and numerical simulation techniques still have shortcomings which are briefly discussed. In this contribution a new universal approach is introduced on how to measure very flexibly multipath propagation effects for arbitrary navigation systems using a channel sounder architecture in a scaled measurement environment. Two relevant scenarios of multipath propagation and the impact on navigation signals are presented. The first describes disturbances of the ILS due to large taxiing aircraft. The other example shows the influence of rotating wind turbines on the VOR.

The macula organ of the labyrinth is stimulated by body roll or translatory movements. Due to its slow development, the salamander Pleurodeles waltl is an excellent model to study the impact of microgravity on the development of the roll-induced vestibuloocular reflex (rVOR) in the absence of any macular stimulation. The experiment was performed during the Soyuz mission TMA8 (return flight TMA7) in 2006 as part of the experiment AMPHIBODY. It was supplemented by a 3g-hypergravity experiment. It was shown, that microgravity retards the over-all development of Pleurodeles tadpoles but not specifically functional development of the vestibular system; normalization took place within 3 to 4 weeks after landing. Hypergravity accelerated rVOR development in the long-term frame.

Microgravity provides unique, though experimentally challenging, opportunities to study motor control. A traditional research focus has been the effects of linear acceleration on vestibular responses to angular acceleration. Evidence is accumulating that the high-frequency vestibulo-ocular reflex (VOR) is not affected by transitions from a 1 g linear force field to microgravity (<1 g); however, it appears that the three-dimensional organization of the VOR is dependent on gravitoinertial force levels. Some of the observed effects of microgravity on head and arm movement control appear to depend on the previously undetected inputs of cervical and brachial proprioception, which change almost immediately in response to alterations in background force levels. Recent studies of post-flight disturbances of posture and locomotion are revealing sensorimotor mechanisms that adjust over periods ranging from hours to weeks.

A series of VOR-DME instrument landing approaches was flown in the DC-9 full-workload simulator to compare pilot performance, scan behavior, and workload when using a computer-drum-pointer altimeter (CDPA) and a digital altimeter (DA). Six pilots executed two sets of instrument landing approaches, with a CDPA on one set and a DA on the other set. Pilot scanning parameters, flight performance, and subjective opinion data were evaluated. It is found that the processes of gathering information from the CDPA and the DA are different. The DA requires a higher mental workload than the CDPA for a VOR-DME type landing approach. Mental processing of altitude information after transitioning back to the attitude indicator is more evident with the DA than with the CDPA.

A semi-circle looped vertically omnidirectional radiation (VOR) patterned tag antenna for UHF (919–923 MHz for Malaysia) frequency is designed to overcome the impedance mismatch issue in this paper. Two impedance matching feeding strips are used in the antenna structure to tune the input impedance of the antenna. Two dipole shaped meandered lines are used to achieve a VOR pattern. The proposed antenna is designed for 23-j224 Ω chip impedance. The antenna is suitable for ‘place and tag’ application. A small size of 77.68×35.5 mm2 is achieved for a read range performance of 8.3 meters using Malaysia regulated maximum power transfer of 2.0 W effective radiated power (ERP). PMID:27533470

A series of VOR-DME instrument landing approaches was flown in the DC-9 full-workload simulator to compare pilot performance, scan behavior, and workload when using a computer-drum-pointer altimeter (CDPA) and a digital altimeter (DA). Six pilots executed two sets of instrument landing approaches, with a CDPA on one set and a DA on the other set. Pilot scanning parameters, flight performance, and subjective opinion data were evaluated. It is found that the processes of gathering information from the CDPA and the DA are different. The DA requires a higher mental workload than the CDPA for a VOR-DME type landing approach. Mental processing of altitude information after transitioning back to the attitude indicator is more evident with the DA than with the CDPA.

This study examined whether the level of victim-offender relationship (VOR) moderated the relationship between peritraumatic fear and active resistance as well as the relationship between peritraumatic fear and posttraumatic stress symptom severity in a community sample of female rape survivors. One hundred thirty-five participants were interviewed about their emotional and behavioral responses during the rape and assessed for posttraumatic stress symptomatology within one month of the assault. Results indicated that peritraumatic fear was positively associated with active resistance, but only among survivors of acquaintance rape. Additionally, peritraumatic fear was positively associated with posttraumatic stress symptom severity, but only among survivors of intimate partner rape. These results suggest that VOR may be an important contextual factor that influences emotional and behavioral responses during rape as well as posttraumatic stress symptomatology in its aftermath. PMID:21731797

Perturbation of semicircular canal function may result in a pathological angular vestibulo-ocular reflex (aVOR). The resulting impairment in gaze stabilization is perceived as "vertigo" or "dizziness" and may occur following receptor function impairment of all three semicircular canals. The head impulse test reveals hidden (covert-catchup) or visible (overt-catchup) saccades in disturbances of semicircular function. Most peripheral vestibular disorders can be treated conservatively. There are surgical treatment options for some diseases, such as intractable benign paroxysmal positional vertigo and superior semicircular canal dehiscence. Vestibular training promotes central reorganization of the VOR. Impaired semicircular receptor function, in particular bilateral vestibulopathy, may affect spatial orientation and cognitive processes. Balance prostheses could serve as a replacement for receptors in the future.

The neural "learning rules" governing the induction of plasticity in the cerebellum were analyzed by recording the patterns of neural activity in awake, behaving animals during stimuli that induce a form of cerebellum-dependent learning. We recorded the simple- and complex-spike responses of a broad sample of Purkinje cells in the floccular complex during a number of stimulus conditions that induce motor learning in the vestibulo-ocular reflex (VOR). Each subclass of Purkinje cells carried essentially the same information about required changes in the gain of the VOR. The correlation of simple-spike activity in Purkinje cells with activity in vestibular pathways could guide learning during low-frequency but not high-frequency stimuli. Climbing fiber activity could guide learning during all stimuli tested but only if compared with the activity present approximately 100 msec earlier in either vestibular pathways or Purkinje cells.

1. The ability of the vestibuloocular reflex (VOR) to undergo adaptive modification after selective changes in the peripheral vestibular system was investigated in rhesus monkeys by recording three-dimensional eye movements before and after inactivation of selective semicircular canals. In the preceding paper we showed that the horizontal VOR gain evoked by passive yaw oscillations after lateral semicircular canal inactivation recovers gradually over time in a frequency-specific manner. Here we present the spatial tuning of the adapted slow-phase eye velocity and describe its spatiotemporal properties as a function of time after canal inactivation. 2. The spatial organization of the VOR was investigated during oscillations at different head positions in the pitch, roll, and yaw planes, as well as in the right anterior/left posterior and left anterior/right posterior canal planes. Acutely after bilateral inactivation of the lateral semicircular canals, a small horizontal response could still be elicited that peaked during rotations in pitched head positions that would maximally stimulate vertical semicircular canals. In addition, the phase of horizontal slow-phase velocity abruptly reversed through 180 degrees at positions close to upright, similarly to torsional slow-phase velocity. These spatial response properties suggest that the small, residual horizontal response components that are present acutely after plugging of both lateral canals originate from vertical semicircular canal signals. 3. As the horizontal response amplitude increased over time, consistent changes were also observed in the spatiotemporal tuning of horizontal slow-phase velocity. 1) The spatiotemporal response properties of horizontal slow-phase velocity acquired noncosine tuning characteristics, primarily in the pitch plane, in the right anterior/left posterior and left anterior/right posterior canal planes. Accordingly, horizontal response amplitude was nonzero during rotation in any head

Astemizole was orally administered to 20 subjects in a randomized, double-blind design to assess the efficacy of this peripherally active antihistamine as an antimotion sickness drug possessing no central side-effects. Measures of vestibular ocular reflex (VOR) were made to evaluate the agent as a selective vestibular depressant. Following one week of orally administered astemizole (30 mg daily), a Staircase Profile Test, a VOR test, and a variety of tests of cognitive performance were administered. These tests revealed no statistically significant effects of astemizole. This leads to the conclusion that, although the drug probably reaches the peripheral vestibular apparatus in man by crossing the blood-vestibular barrier, a selective peripheral antihistamine (H1) action is inadequate to control motion sickness induced through cross-coupled accelerative semicircular canal stimulation in a rotating chair.

A semi-circle looped vertically omnidirectional radiation (VOR) patterned tag antenna for UHF (919-923 MHz for Malaysia) frequency is designed to overcome the impedance mismatch issue in this paper. Two impedance matching feeding strips are used in the antenna structure to tune the input impedance of the antenna. Two dipole shaped meandered lines are used to achieve a VOR pattern. The proposed antenna is designed for 23-j224 Ω chip impedance. The antenna is suitable for 'place and tag' application. A small size of 77.68×35.5 mm2 is achieved for a read range performance of 8.3 meters using Malaysia regulated maximum power transfer of 2.0 W effective radiated power (ERP).

The effects of air, helium-oxygen (6.4 ATA), and ethyl alcohol (40% by volume at a dose of 1.5 ml/kg body weight) were examined on the gain, number of beats, and phase lag of the vestibular ocular reflex (VOR) by means of electronystagmography (n = 7). It was found that hyperbaric air and alcohol, both alone and in combination, produced approximately the same increase in the velocity of the slow phase component of the nystagmus, thereby elevating the gain of the system to unity. Hyperbaric helium-oxygen did not influence the gain. These findings suggest that nitrogen nacrosis differentially impairs the system controlling the VOR. It is proposed that this impairment may help to explain the disorientation sometimes associated with nitrogen narcosis.

Loran-C time-difference data were collected on January 9, 1979 during a flight from Athens, Ohio to Madison VOR in Connecticut, thence to Millville VOR in New Jersey, and a landing at Atlantic City NAFEC. Portions of the return trip to Athens, Ohio were also recorded. Loran-C GRI data frames were recorded using the 99600 U. S. Northeast Loran chain stations Seneca/Nantucket (TDA) and Seneca/Carolina Beach (TDB). The GRI sequence number TDA and TDB were recorded as integer numbers, with the TD's in integer microseconds. Actual time-of-day can be determined from the data start time, plus the time per GRI and the sequence number. The low cost Loran-C receiver was used to obtain the time-difference data for each GRI. Data was recorded on digital magnetic tape and post-processed into latitude and longitude using an IBM system/370 computer.

The horizontal vestibulo-ocular reflex (VOR) was measured and characterized in seven adult chinchillas using 0.01 to 1.0 Hz angular velocity sinusoids. Gains were less than compensatory, and were variable from day to day, but phases were highly repeatable both within and between animals. The best fitting transfer function to the average data of all animals had a dominant time constant of 7.5 sec, and an adaptation operator with a time constant of 24.0 sec. There were certain nonlinearities in the horizontal VOR of this animal, and it was difficult to elicit a robust optokinetic response. Results are discussed in relation to similar measurements in other species.

Corl, and Jensen, 1981). These advances in avionics capabilities, especially the explosion in low-cost, light-weight, and highly reliable computing...waypoints, VOR and TACAN information, course lines, deviation from desired course (and flight path prediction in some cases), time and distance to...display was developed such tizat control and display dynamics are directionally compatible. He als) provided flight prediction in both the horizontal

The angular vestibulo-ocular reflex (aVOR) has a fast pathway, which mediates compensatory eye movements, and a slow (velocity storage) pathway, which determines its low frequency characteristics and orients eye velocity toward gravity. We have proposed that motion sickness is generated through velocity storage, when its orientation vector, which lies close to the gravitational vertical, is misaligned with eye velocity during head motion. The duration of the misalignment, determined by the dominant time constant of velocity storage, causes the buildup of motion sickness. To test this hypothesis, we studied bilateral labyrinthine-defective subjects with short vestibular time constants but normal aVOR gains for their motion sickness susceptibility. Time constants and gains were taken from rotational responses. Motion sickness was generated by rolling the head while rotating, and susceptibility was assessed by the number of head movements made before reaching intolerable levels of nausea. More head movements signified lower motion sickness susceptibility. Labyrinthine-defective subjects made more head movements on their first exposure to roll while rotating than normals (39.8 +/- 7.2 vs 13.7 +/- 5.5; P < 0.0001). Normals were tested eight times, which habituated their time constants and reduced their motion sickness susceptibility. Combining data from all subjects, there was a strong inverse relationship between time constants and number of head movements (r = 0.94), but none between motion sickness susceptibility and aVOR gains. This provides further evidence that motion sickness is generated through velocity storage, not the direct pathway, and suggests that motion sickness susceptibility can be reduced by reducing the aVOR time constant.

TBI survi- vors is pathophysiologically similar to Alzheimer disease, CTE, or some other entity. Such infor- mation is critical for developing...pathophysiologically similar to Alzheimer disease, CTE, or some other entity. Such information is critical for developing preventive and treatment strategies for a...the epidemio- logic studies regarding specific clinical features of de- mentia associated with TBI. Most studies have focused on Alzheimer disease (AD

This proposal had the long-term objective of examining the effects of microgravity on the physiology of the adult and developing mammalian gravity receptors. The grant outlined three-years of ground-based studies to examine. 1) the physiologic responses or otolith afferents in the adult rat and during postnatal development, and 2) the otolith organ contributions to the vertical vestibulo-ocular (VOR) and postural reflexes.

Hypothesis As the anterior and posterior semicircular canals are vital to the regulation of gaze stability, particularly during locomotion or vehicular travel, we tested whether the high velocity vestibulo-ocular reflex (VOR) of the three ipsilesional semicircular canals elicited by the modified Head Impulse Test would correlate with subjective dizziness or vertigo scores after vestibular neuritis (VN). Background Recovery following acute VN varies with around half reporting persistent symptoms long after the acute episode. However, an unanswered question is whether chronic symptoms are associated with impairment of the high velocity VOR of the anterior or posterior canals. Methods Twenty patients who had experienced an acute episode of VN at least three months earlier were included in this study. Participants were assessed with the video head impulse test (vHIT) of all six canals, bithermal caloric irrigation, the Dizziness Handicap Inventory (DHI) and the Vertigo Symptoms Scale short-form (VSS). Results Of these 20 patients, 12 felt that they had recovered from the initial episode whereas 8 did not and reported elevated DHI and VSS scores. However, we found no correlation between DHI or VSS scores and the ipsilesional single or combined vHIT gain, vHIT gain asymmetry or caloric paresis. The high velocity VOR was not different between patients who felt they had recovered and patients who felt they had not. Conclusions Our findings suggest that chronic symptoms of dizziness following VN are not associated with the high velocity VOR of the single or combined ipsilesional horizontal, anterior or posterior semicircular canals. PMID:26719963

Purpose While an ideal vestibulo-ocular reflex (VOR) generates ocular rotations compensatory for head motion, during visually guided movements, Listing’s Law (LL) constrains the eye to rotational axes lying in Listing’s Plane (LP). The present study was conducted to explore the recent proposal that the VOR’s rotational axis is not collinear with the head’s, but rather follows a time-dependent strategy intermediate between LL and an ideal VOR. Methods Binocular LPs were defined during visual fixation in eight normal humans. The VOR was evoked by a highly repeatable transient whole-body yaw rotation in darkness at a peak acceleration of 2800 deg/s2. Immediately before rotation, subjects regarded targets 15 or 500 cm distant located at eye level, 20° up, or 20° down. Eye and head responses were compared with LL predictions in the position and velocity domains. Results LP orientation varied both among subjects and between individual subject’s eyes, and rotated temporally with convergence by 5 ± 5° (±SEM). In the position domain, the eye compensated for head displacement even when the head rotated out of LP. Even within the first 20 ms from onset of head rotation, the ocular velocity axis tilted relative to the head axis by 30% ± 8% of vertical gaze position. Saccades increased this tilt. Regardless of vertical gaze position, the ocular rotation axis tilted backward 4° farther in abduction than in adduction. There was also a binocular vertical eye velocity transient and lateral tilt of the ocular axis. Conclusions These disconjugate, short-latency axis perturbations appear intrinsic to the VOR and may have neural or mechanical origins. PMID:16565376

Vestibulo-ocular reflexes (VOR) ensure gaze stability during locomotion and passively induced head/body movements. In precocial vertebrates such as amphibians, vestibular reflexes are required very early at the onset of locomotor activity. While the formation of inner ears and the assembly of sensory-motor pathways is largely completed soon after hatching, angular and translational/tilt VOR display differential functional onsets and mature with different time courses. Otolith-derived eye movements appear immediately after hatching, whereas the appearance and progressive amelioration of semicircular canal-evoked eye movements is delayed and dependent on the acquisition of sufficiently large semicircular canal diameters. Moreover, semicircular canal functionality is also required to tune the initially omnidirectional otolith-derived VOR. The tuning is due to a reinforcement of those vestibulo-ocular connections that are co-activated by semicircular canal and otolith inputs during natural head/body motion. This suggests that molecular mechanisms initially guide the basic ontogenetic wiring, whereas semicircular canal-dependent activity is required to establish the spatio-temporal specificity of the reflex. While a robust VOR is activated during passive head/body movements, locomotor efference copies provide the major source for compensatory eye movements during tail- and limb-based swimming of larval and adult frogs. The integration of active/passive motion-related signals for gaze stabilization occurs in central vestibular neurons that are arranged as segmentally iterated functional groups along rhombomere 1–8. However, at variance with the topographic maps of most other sensory systems, the sensory-motor transformation of motion-related signals occurs in segmentally specific neuronal groups defined by the extraocular motor output targets. PMID:27877114

frequency (RF) aids: the Global Positioning System (GPS), TACAN, VOR/DME, etc., which evolved from RF navigation systems, such as Gee and LORAN ...solutions to enhance efficiency and exploit source diversity 3) Promote, where appropriate, fusion of PNT with new and evolving communications... enhancements will result in greater capabilities that will be more commonly available. 2. Monitor PNT signals to verify service levels, observe

Model simulations of the squirrel monkey vestibulo-ocular reflex (VOR) are presented for two motion paradigms: constant velocity eccentric rotation and roll tilt about a naso-occipital axis. The model represents the implementation of three hypotheses: the "internal model" hypothesis, the "gravito-inertial force (GIF) resolution" hypothesis, and the "compensatory VOR" hypothesis. The internal model hypothesis is based on the idea that the nervous system knows the dynamics of the sensory systems and implements this knowledge as an internal dynamic model. The GIF resolution hypothesis is based on the idea that the nervous system knows that gravity minus linear acceleration equals GIF and implements this knowledge by resolving the otolith measurement of GIF into central estimates of gravity and linear acceleration, such that the central estimate of gravity minus the central estimate of acceleration equals the otolith measurement of GIF. The compensatory VOR hypothesis is based on the idea that the VOR compensates for the central estimates of angular velocity and linear velocity, which sum in a near-linear manner. During constant velocity eccentric rotation, the model correctly predicts that: (1) the peak horizontal response is greater while "facing-motion" than with "back-to-motion"; (2) the axis of eye rotation shifts toward alignment with GIF; and (3) a continuous vertical response, slow phase downward, exists prior to deceleration. The model also correctly predicts that a torsional response during the roll rotation is the only velocity response observed during roll rotations about a naso-occipital axis. The success of this model in predicting the observed experimental responses suggests that the model captures the essence of the complex sensory interactions engendered by eccentric rotation and roll tilt.

Optical reversal of vision brings about adaptive changes in the vestibulo-ocular reflex (VOR) tending to reduce retinal image slip during head movement. The present experiments investigated this form of adaptation in cats whose complement of direction sensitive central visual cells had been substantially reduced by rearing in 8 Hz stroboscopic light. Horizontal vision reversal was produced by dove prisms carried in a skull-mounted mask. A scleral eye coil was used to measure horizontal eye movements. VOR gain and phase were measured in the dark during sinusoidal rotation using test stimuli of 1/8 Hz and 5- or 20 degrees/sec velocity amplitude. Initially, strobe reared cats produced virtually normal VOR in the dark, except for slight but significant exaggeration of the normal phase advancement to be expected at 1/8 Hz. Addition of their familiar strobe illumination produced almost perfect oculomotor compensation. Maintained vision reversal in both strobe and normal illumination produced similar patterns of adaptive change in normal and strobe reared subjects, i.e. all animals exhibited an initial fast, and subsequent much slower, stage of gain attenuation, with similar changes in phase. Thus, strobe rearing did not prevent the development of an essentially normal VOR, nor did it interfere significantly with the ability to adapt in response to vision reversal. Since strobe rearing depletes direction selective visual movement detectors in the cortex and superior colliculi, it is inferred that signals responsible for activating the adaptive process are probably carried mainly in the accessory optic, rather than cortical and collicular, visual system.

The mal de debarquement syndrome (MdDS), a continuous feeling of swaying, rocking, and/or bobbing, generally follows travel on the sea. The associated symptoms cause considerable distress. The underlying neural mechanisms are unknown, and to date there have been no effective treatments for this condition. Results in monkeys and humans suggested that MdDS was caused by maladaptation of the vestibulo-ocular reflex (VOR) to roll of the head during rotation. We studied 24 subjects with persistent MdDS (3 males, 21 females; 19.1 ± 33 months). Physical findings included body oscillation at 0.2 Hz, oscillating vertical nystagmus when the head was rolled from side-to-side in darkness, and unilateral rotation during the Fukuda stepping test. We posited that the maladapted rocking and the physical symptoms could be diminished or extinguished by readapting the VOR. Subjects were treated by rolling the head from side-to-side while watching a rotating full-field visual stimulus. Seventeen of the 24 subjects had a complete or substantial recovery on average for approximately 1 year. Six were initially better, but the symptoms recurred. One subject did not respond to treatment. Thus, readaptation of the VOR has led to a cure or substantial improvement in 70% of the subjects with MdDS. We conclude that the adaptive processes associated with roll-while-rotating are responsible for producing MdDS, and that the symptoms can be reduced or resolved by readapting the VOR.

A neural network model was developed to explain the gravity-dependent properties of gain adaptation of the angular vestibuloocular reflex (aVOR). Gain changes are maximal at the head orientation where the gain is adapted and decrease as the head is tilted away from that position and can be described by the sum of gravity-independent and gravity-dependent components. The adaptation process was modeled by modifying the weights and bias values of a three-dimensional physiologically based neural network of canal-otolith-convergent neurons that drive the aVOR. Model parameters were trained using experimental vertical aVOR gain values. The learning rule aimed to reduce the error between eye velocities obtained from experimental gain values and model output in the position of adaptation. Although the model was trained only at specific head positions, the model predicted the experimental data at all head positions in three dimensions. Altering the relative learning rates of the weights and bias improved the model-data fits. Model predictions in three dimensions compared favorably with those of a double-sinusoid function, which is a fit that minimized the mean square error at every head position and served as the standard by which we compared the model predictions. The model supports the hypothesis that gravity-dependent adaptation of the aVOR is realized in three dimensions by a direct otolith input to canal-otolith neurons, whose canal sensitivities are adapted by the visual-vestibular mismatch. The adaptation is tuned by how the weights from otolith input to the canal-otolith-convergent neurons are adapted for a given head orientation.

Next Generation Life Support (NGLS) is one of several technology development projects sponsored by NASA s Game Changing Development Program. The NGLS Project is developing life support technologies (including water recovery and space suit life support technologies) needed for humans to live and work productively in space. NGLS has three project tasks: Variable Oxygen Regulator (VOR), Rapid Cycle Amine (RCA) swing bed, and Alternative Water Processor (AWP). The RCA swing bed and VOR tasks are directed at key technology needs for the Portable Life Support System (PLSS) for an Advanced Extravehicular Mobility Unit, with focus on test article development and integrated testing in an Advanced PLSS in cooperation with the Advanced Extra Vehicular Activity (EVA) Project. An RCA swing-bed provides integrated carbon dioxide removal and humidity control that can be regenerated in real time during an EVA. The VOR technology will significantly increase the number of pressure settings available to the space suit. Current space suit pressure regulators are limited to only two settings whereas the adjustability of the advanced regulator will be nearly continuous. The AWP effort, based on natural biological processes and membrane-based secondary treatment, will result in the development of a system capable of recycling wastewater from sources expected in future exploration missions, including hygiene and laundry water. This paper will provide a status of technology development activities and future plans.

Fungisome(TM) is a liposomal preparation of amphotericin B (AMB), already marketed in India. However, its antifungal activity has not been evaluated against a wide range of fungal pathogens. The study was planned to elucidate the in vitro antifungal activity of Fungisome(TM) against wide range of fungi and compare it with AMB deoxycholate (AMB-d), voriconazole (VOR), itraconazole (ITR) and fluconazole (FLU). Minimum inhibitory concentrations (MICs) of the drugs were determined for 262 clinical fungal isolates, including yeast, dimorphic and filamentous fungi, by broth microdilution method approved by Clinical and Laboratory Standards Institute, USA (yeast, M27-A3; filamentous fungi, M38-A2). The MIC(90s) of Fungisome(TM) were 0.125, 0.5 and 0.25 mg l(-1) against yeast, filamentous and dimorphic fungi respectively. In comparison, MIC(90s) of AMB-d, FLU, ITR and VOR were 1, 1 and 1 mg l(-1) (AMB-d), 4, 64 and 64 mg l(-1) (FLU), 1, 16 and 16 mg l(-1) (ITR) and 0.5, 4 and 16 mg l(-1) (VOR) against yeast, filamentous and dimorphic fungi respectively. The MIC of Fungisome(TM) was two to 16-fold lower than AMB-d. These results reveal an efficient in vitro activity of Fungisome(TM).

Azoles are antifungal drugs used to treat fungal infections such as candidiasis in humans. Their extensive use has led to the emergence of drug resistance, complicating antifungal therapy for yeast infections in critically ill patients. Combination therapy has become popular in clinical practice as a potential strategy to fight resistant fungal isolates. Recently, amphiphilic tobramycin analogues, C12 and C14, were shown to display antifungal activities. Herein, the antifungal synergy of C12 and C14 with four azoles, fluconazole (FLC), itraconazole (ITC), posaconazole (POS), and voriconazole (VOR), was examined against seven Candida albicans strains. All tested strains were synergistically inhibited by C12 when combined with azoles, with the exception of C. albicans 64124 and MYA-2876 by FLC and VOR. Likewise, when combined with POS and ITC, C14 exhibited synergistic growth inhibition of all C. albicans strains, except C. albicans MYA-2876 by ITC. The combinations of FLC-C14 and VOR-C14 showed synergistic antifungal effect against three C. albicans and four C. albicans strains, respectively. Finally, synergism between C12/C14 and POS were confirmed by time-kill and disk diffusion assays. These results suggest the possibility of combining C12 or C14 with azoles to treat invasive fungal infections at lower administration doses or with a higher efficiency. PMID:26594050

Our sense of self-motion and self-orientation results from combining information from different sources. We hypothesize that the central nervous system (CNS) uses internal models of the laws of physics to merge cues provided by different sensory systems. Different models that include internal models have been proposed; we focus herein on that referred to as the sensory weighting model (Zupan et al 2002 Biol. Cybern. 86 209-30). For simplicity, we isolate the portion of the sensory weighting model that estimates head angular velocity: it includes an inverse internal model of head kinematics and an 'idiotropic' vector aligned with the main body axis. Following a post-rotatory tilt in the dark, which is a rapid tilt following a constant-velocity rotation about an earth-vertical axis, the inverse internal model is applied to conflicting vestibular signals. Consequently, the CNS computes an inaccurate estimate of head angular velocity that shifts toward alignment with an estimate of gravity. Since reflexive eye movements known as vestibulo-ocular reflexes (VOR) compensate for this estimate of head angular velocity, the model predicts that the VOR rotation axis shifts toward alignment with this estimate of gravity and that the VOR time constant depends on final head orientation. These predictions are consistent with experimental data.

The head-impulse test (HIT) is an important test for examining unilateral vestibular hypofunction. The new video-head-impulse test (vHIT) is more sensitive and specific than the clinical bedside-head-impulse test. Alternatively, one can test for vestibular hypofunction with the caloric irrigation test. Various studies have shown that both tests may not always identify vestibular hypofunction; instead, the results of the tests might be contradictory. To further explore the question, of whether vHIT and caloric irrigation test the same part of the angular horizontal vestibulo-ocular reflex (VOR), we examined patients with unilateral vestibular neuritis at different points in time. The tonic vestibular imbalance (e.g., subjective-visual-vertical, ocular torsion and spontaneous nystagmus) and dynamic dysfunction of VOR (vHIT and bithermal caloric irrigation) were measured and quantified. While parameters of the tonic vestibular imbalance were well described by single exponential decay functions, dynamic parameters were less well defined. Therefore, to better compare the time course of pairs of two different parameters, we used a linear regression analysis. No linear correlation was found in the group and individually for the gain asymmetry and the ipsilesional gain of the vHIT with the unilateral weakness of the bithermal caloric irrigation tests. Linear correlation was found for most parameters of tonic vestibular imbalance. These findings are further evidence that vHIT and caloric irrigation test different parts of the angular VOR.

Developmental and evolutionary data from vertebrates are beginning to elucidate the origin of the sensorimotor pathway that links gravity and motion detection to image-stabilizing eye movements--the vestibulo-ocular reflex (VOR). Conserved transcription factors coordinate the development of the vertebrate ear into three functional sensory compartments (graviception/translational linear acceleration, angular acceleration and sound perception). These sensory components connect to specific populations of vestibular and auditory projection neurons in the dorsal hindbrain through undetermined molecular mechanisms. In contrast, a molecular basis for the patterning of the vestibular projection neurons is beginning to emerge. These are organized through the actions of rostrocaudally and dorsoventrally restricted transcription factors into a 'hodological mosaic' within which coherent and largely segregated subgroups are specified to project to different targets in the spinal cord and brain stem. A specific set of these regionally diverse vestibular projection neurons functions as the central element that transforms vestibular sensory signals generated by active and passive head and body movements into motor output through the extraocular muscles. The large dynamic range of motion-related sensory signals requires an organization of VOR pathways as parallel, frequency-tuned, hierarchical connections from the sensory periphery to the motor output. We suggest that eyes, ears and functional connections subserving the VOR are vertebrate novelties that evolved into a functionally coherent motor control system in an almost stereotypic organization across vertebrate taxa.

New evidence for a central resolution of gravito-inertial signals has been recently obtained by analyzing the properties of the vestibulo-ocular reflex (VOR) in response to combined lateral translations and roll tilts of the head. It is found that the VOR generates robust compensatory horizontal eye movements independent of whether or not the interaural translatory acceleration component is canceled out by a gravitational acceleration component due to simultaneous roll-tilt. This response property of the VOR depends on functional semicircular canals, suggesting that the brain uses both otolith and semicircular canal signals to estimate head motion relative to inertial space. Vestibular information about dynamic head attitude relative to gravity is the basis for computing head (and body) angular velocity relative to inertial space. Available evidence suggests that the inertial vestibular system controls both head attitude and velocity with respect to a gravity-centered reference frame. The basic computational principles underlying the inertial processing of otolith and semicircular canal afferent signals are outlined.

Three-dimensional squirrel monkey eye movements were recorded during and immediately following rotation around an earth-vertical yaw axis (160 degrees/s steady state, 100 degrees/s2 acceleration and deceleration). To study interactions between the horizontal angular vestibulo-ocular reflex (VOR) and head orientation, postrotatory VOR alignment was changed relative to gravity by tilting the head out of the horizontal plane (pitch or roll tilt between 15 degrees and 90 degrees) immediately after cessation of motion. Results showed that in addition to post rotatory horizontal nystagmus, vertical nystagmus followed tilts to the left or right (roll), and torsional nystagmus followed forward or backward (pitch) tilts. When the time course and spatial orientation of eye velocity were considered in three dimensions, the axis of eye rotation always shifted toward alignment with gravity, and the postrotatory horizontal VOR decay was accelerated by the tilts. These phenomena may reflect a neural process that resolves the sensory conflict induced by this postrotatory tilt paradigm.

The ability to simultaneously move in the world and maintain stable visual perception depends critically on the contribution of vestibulo-ocular reflexes (VORs) to gaze stabilization. It is traditionally believed that semicircular canal signals drive compensatory responses to rotational head disturbances (rotational VOR), whereas otolith signals compensate for translational movements [translational VOR (TVOR)]. However, a sensory ambiguity exists because otolith afferents are activated similarly during head translations and reorientations relative to gravity (i.e., tilts). Extra-otolith cues are, therefore, necessary to ensure that dynamic head tilts do not elicit a TVOR. To investigate how extra-otolith signals contribute, we characterized the temporal and viewing distance-dependent properties of a TVOR elicited in the absence of a lateral acceleration stimulus to the otoliths during combined translational/rotational motion. We show that, in addition to otolith signals, angular head position signals derived by integrating sensory canal information drive the TVOR. A physiological basis for these results is proposed in a model with two distinct integration steps. Upstream of the well known oculomotor velocity-to-position neural integrator, the model incorporates a separate integration element that could represent the "velocity storage integrator," whose functional role in the oculomotor system has so far remained controversial. We propose that a key functional purpose of the velocity storage network is to temporally integrate semicircular canal signals, so that they may be used to extract translation information from ambiguous otolith afferent signals in the natural and functionally relevant bandwidth of head movements.

In this paper, a model of cerebellar function is implemented and evaluated in the control of a robot eye actuated by pneumatic artificial muscles. The investigated control problem is stabilization of the visual image in response to disturbances. This is analogous to the vestibuloocular reflex (VOR) in humans. The cerebellar model is structurally based on the adaptive filter, and the learning rule is computationally analogous to least-mean squares, where parameter adaptation at the parallel fiber/Purkinje cell synapse is driven by the correlation of the sensory error signal (carried by the climbing fiber) and the motor command signal. Convergence of the algorithm is first analyzed in simulation on a model of the robot and then tested online in both one and two degrees of freedom. The results show that this model of neural function successfully works on a real-world problem, providing empirical evidence for validating: 1) the generic cerebellar learning algorithm; 2) the function of the cerebellum in the VOR; and 3) the signal transmission between functional neural components of the VOR.

In Xenopus laevis tadpoles, we studied the static vestibuloocular reflex (rVOR) in relation to modifications of the gravitational environment to find basic mechanisms of how altered gravitational forces (AGF) affect this reflex. Animals were exposed to microgravity during space flight or hypergravity (3g) for 4 to 12 days. Basic observations were that (1) the development of the rVOR is significantly affected by altered gravitational conditions, (2) the duration of 1g-readaptation depends on the strength of the test stimulus, (3) μg induces malformations of the body which are related to the rVOR depression. Future studies are based on the hypotheses (1) that the vestibular nuclei play a key roll in the adaptation to AGF conditions, (2) that the stimulus transducing systems in the sense organ are affected by AGF conditions, and (3) that fertilized eggs will be converted to normal adults guided by physiological and morphological set points representing the genetic programs. Developmental retardation or acceleration, or otherwise occurring deviations from standard development during embryonic and postembryonic life will activate genes that direct the developmental processes towards normality.

The effects of unilateral labyrinthectomy on the properties of the translational vestibuloocular reflexes (trVORs) were investigated in rhesus monkeys trained to fixate near targets. Translational motion stimuli consisted of either steady-state lateral and fore-aft sinusoidal oscillations or short-lasting transient displacements. During small-amplitude, steady-state sinusoidal lateral oscillations, a small decrease in the horizontal trVOR sensitivity and its dependence on viewing distance was observed during the first week after labyrinthectomy. These deficits gradually recovered over time. In addition, the vertical response component increased, causing a tilt of the eye velocity vector toward the lesioned side. During large, transient lateral displacements, the deficits were larger and longer lasting. Responses after labyrinthectomy were asymmetric, with eye velocity during movements toward the side of the lesion being more compromised. The most profound effect of the lesions was observed during fore-aft motion. Whereas responses were kinematically appropriate for fixation away from the side of the lesion (e.g., to the left after right labyrinthectomy), horizontal responses were anticompensatory during fixation at targets located ipsilateral to the side of the lesion (e.g., for targets to the right after right labyrinthectomy). This deficit showed little recovery during the 3-mo post-labyrinthectomy testing period. These results suggest that inputs from both labyrinths are important for the proper function of the trVORs, although the details of how bilateral signals are processed and integrated remain unknown.

In two experiments, we examined the possibility that the human vestibulo-ocular reflex (VOR) is subject to dual adaptation (the ability to adapt to a sensory rearrangement more rapidly and/or more completely after repeated experience with it) and adaptive generalization (the ability to adapt more readily to a novel sensory rearrangement as a result of prior dual adaptation training). In Experiment 1, the subjects actively turned the head during alternating exposure to a visual-vestibular rearrangement (target/head gain = 0.5) and the normal situation (target/head gain = 0.0). These conditions produced both adaptation and dual adaptation of the VOR but no evidence of adaptive generalization when tested with a target/head gain of 1.0. Experiment 2, in which exposure to the 0.5 gain entailed externally controlled (i.e., passive) whole body rotation, resulted in VOR adaptation but no dual adaptation. As in Experiment 1, no evidence of adaptive generalization was found.

The dynamics and three-dimensional (3-D) properties of the primate translational vestibuloocular reflex (trVOR) for high-frequency (4-12 Hz, +/-0.3-0.4 g) lateral motion were investigated during near-target viewing at center and eccentric targets. Horizontal response gains increased with frequency and depended on target eccentricity. The larger the horizontal and vertical target eccentricity, the steeper the dependence of horizontal response gain on frequency. In addition to horizontal eye movements, robust torsional response components also were present at all frequencies. During center-target fixation, torsional response phase was opposite (anticompensatory) to that expected for an "apparent" tilt response. Instead torsional response components depended systematically on vertical-target eccentricity, increasing in amplitude when looking down and reversing phase when looking up. As a result the trVOR eye velocity vector systematically tilted away from a purely horizontal direction, through an angle that increased with vertical eccentricity with a slope of approximately 0.7. This systematic dependence of torsional eye velocity tilt on vertical eye position suggests that the trVOR might follow the 3-D kinematic requirements that have been shown to govern visually guided eye movements and near-target fixation.

During locomotion, there is a translation and compensatory rotation of the head in both the vertical and horizontal planes. During moderate to fast walking (100 m/min), vertical head translation occurs at the frequency of stepping (2 Hz) and generates peak linear acceleration of 0.37 g. Lateral head translation occurs at the stride frequency (1 Hz) and generates peak linear acceleration of 0.1 g. Peak head pitch and yaw angular velocities are approximately 17 degrees/s. The frequency and magnitude of these head movements are within the operational range of both the linear and angular vestibulo-ocular reflex (IVOR and aVOR). Vertical eye movements undergo a phase reversal from near to far targets. When viewing a far (>1 m) target, vertical eye velocity is typical of an aVOR response; that is, it is compensatory for head pitch. At close viewing distances (<1 m), vertical eye velocity is in phase with head pitch and is compensatory for vertical head translation, suggesting that the IVOR predominantly generates the eye movement response. Horizontal head movements during locomotion occur at the stride frequency of 1 Hz, where the IVOR gain is low. Horizontal eye movements are compensatory for head yaw at all viewing distances and are likely generated by the aVOR.

The effects of functional, reversible ablation and potential recruitment of the most irregular otolith afferents on the dynamics and sensitivity of the translational vestibuloocular reflexes (trVORs) were investigated in rhesus monkeys trained to fixate near and far targets. Translational motion stimuli consisted of either steady-state lateral and fore-aft sinusoidal oscillations or short-lasting transient lateral head displacements. Short-duration (usually <2 s) anodal (inhibitory) and cathodal (excitatory) currents (50-100 microA) were delivered bilaterally during motion. In the presence of anodal labyrinthine stimulation, trVOR sensitivity and its dependence on viewing distance were significantly decreased. In addition, anodal currents significantly increased phase lags. During transient motion, anodal stimulation resulted in significantly lower initial eye acceleration and more sluggish responses. Cathodal currents tended to have opposite effects. The main characteristics of these results were simulated by a simple model where both regularly and irregularly discharging afferents contribute to the trVORs. Anodal labyrinthine currents also were found to decrease eye velocity during long-duration, constant velocity rotations, although results were generally more variable compared with those during translational motion.

The vestibuloocular reflex (VOR) of two rhesus monkeys was recorded before and after 14 days of spaceflight. The gain (eye velocity/head velocity) of the horizontal VOR, tested 15 and 18 h after landing, was approximately equal to preflight values. The dominant time constant of the animal tested 15 h after landing was equivalent to that before flight. During nystagmus induced by off-vertical axis rotation (OVAR), the latency, rising time constant, steady-state eye velocity, and phase of modulation in eye velocity and eye position with respect to head position were similar in both monkeys before and after flight. There were changes in the amplitude of modulation of horizontal eye velocity during steady-state OVAR and in the ability to discharge stored activity rapidly by tilting during postrotatory nystagmus (tilt dumping) after flight: OVAR modulations were larger, and tilt dumping was lost in the one animal tested on the day of landing and for several days thereafter. If the gain and time constant of the horizontal VOR exchange in microgravity, they must revert to normal soon after landing. The changes that were observed suggest that adaptation to microgravity had caused alterations in way that the central nervous system processes otolith input.

In spinocerebellar ataxia type 6 (SCA6), the vestibular dysfunction and its correlation with other clinical parameters require further exploration. We determined vestibular responses over a broad range of stimulus acceleration in 11 patients with SCA6 (six men, age range=33-72 years, mean age±SD=59±12 years) using bithermal caloric irrigations, rotary chair, and head impulse tests. Correlations were also pursued among disability scores, as measured using the International Cooperative Ataxia Rating Scale, disease duration, age at onset, cytosine-adenine-guanine (CAG) repeat length, and the gain of the vestibulo-ocular reflex (VOR). In response to relatively low-acceleration, low-frequency rotational and bithermal caloric stimuli, the VOR gains were normal or increased regardless of the severity of disease. On the other hand, with relatively high-acceleration, high-frequency head impulses, there was a relative increase in gain in the mildly affected patients and a decrease in gain in the more severely affected patients and gains were negatively correlated with the severity of disease (Spearman correlation, R=-0.927, p<0.001). Selective decrease of the vestibular responses during high-acceleration, high-frequency stimuli may be ascribed to degeneration of either the flocculus or vestibular nuclei. The performance of the VOR during high-acceleration, high-frequency head impulses may be a quantitative indicator of clinical decline in SCA6.

Long-term depression (LTD) at excitatory synapses between parallel fibers and a Purkinje cell has been regarded as a critical cellular mechanism for motor learning. However, it was demonstrated that normal motor learning occurs under LTD suppression, suggesting that cerebellar plasticity mechanisms other than LTD also contribute to motor learning. One candidate for such plasticity is rebound potentiation (RP), which is long-term potentiation at inhibitory synapses between a stellate cell and a Purkinje cell. Both LTD and RP are induced by the increase in postsynaptic Ca(2+) concentration, and work to suppress the activity of a Purkinje cell. Thus, LTD and RP might work synergistically, and one might compensate defects of the other. RP induction is dependent on the interaction between GABAA receptor and GABAA receptor binding protein (GABARAP). Transgenic mice expressing a peptide which inhibits binding of GABARAP and GABAA receptor only in Purkinje cells show defects in both RP and adaptation of vestibulo-ocular reflex (VOR), a motor learning paradigm. However, another example of motor learning, adaptation of optokinetic response (OKR), is normal in the transgenic mice. Both VOR and OKR are reflex eye movements suppressing the slip of visual image on the retina during head movement. Previously, we reported that delphilin knockout mice show facilitated LTD induction and enhanced OKR adaptation, but we recently found that VOR adaptation was not enhanced in the knockout mice. These results together suggest that animals might use LTD and RP differently depending on motor learning tasks.

Oxcarbazepine (OXC), a second-generation antiepileptic drug, undergoes rapid reduction with formation of the active metabolite 10,11-dihydro-10-hydroxy-carbazepine (MHD) in vivo. In this study, a method for simultaneous determination of OXC and MHD in rat plasma using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS-MS) was developed and validated. Under given chromatographic conditions, OXC, MHD and internal standard diazepam were separated well and quantified by electrospray positive ionization mass spectrometry in the multiple reaction monitoring transitions mode. The method validation demonstrated good linearity over the range of 10-2,000 ng/mL for OXC and 5-1,000 ng/mL for MHD. The lower limit of quantification was 5 ng/mL for OXC and 2.5 ng/mL for MHD, respectively. The method was successfully applied to the evaluation of the pharmacokinetics of OXC and MHD in rats, with or without pretreatment by ketoconazole (KET) and voriconazole (VOR). Statistics indicated that KET and VOR significantly affected the disposition of OXC and MHD in vivo, whereas VOR predominantly interfered with the disposition of MHD. This method is suitable for pharmacokinetic study in small animals.

The purpose of this study was to determine adaptations in head stability resulting from altered gaze control and vision during over-ground walking. Using over-ground walking permitted adaptations in walking velocity and cadence that are otherwise not possible during treadmill walking or walking-in-place. Gaze control and vision were manipulated by having 20 young adult subjects 1) walk naturally, 2) view a distant, earth-fixed target to enhance the vestibulo-ocular reflex (VOR), 3) view a head-fixed target to suppress the VOR, and 4) walk in darkness. Horizontal head and trunk angular velocities in space, walking velocity and cadence were measured. Root-mean-square head and trunk angular velocities were calculated and frequency analyses determined head-trunk movement patterns. Results demonstrated that when given the opportunity, subjects slowed down and decreased cadence in response to challenging tasks. Despite strongly reduced walking velocity and cadence, walking in darkness proved most challenging for head stabilization, indicating the importance of vision during this process. Viewing the earth-fixed target demonstrated the greatest head stability thereby, facilitating gaze stabilization. However, comparisons between the earth-fixed and head-fixed target conditions suggest a reciprocal relationship where gaze stability also facilitates head stability. This contribution of gaze stability to head stability is more important than vision alone as the head stabilization response was diminished during the VOR suppressed condition.

Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.

Angelman syndrome (AS) is a severe neurological disorder that is associated with prominent movement and balance impairments that are widely considered to be due to defects of cerebellar origin. Here, using the cerebellar-specific vestibulo-ocular reflex (VOR) paradigm, we determined that cerebellar function is only mildly impaired in the Ube3am–/p+ mouse model of AS. VOR phase-reversal learning was singularly impaired in these animals and correlated with reduced tonic inhibition between Golgi cells and granule cells. Purkinje cell physiology, in contrast, was normal in AS mice as shown by synaptic plasticity and spontaneous firing properties that resembled those of controls. Accordingly, neither VOR phase-reversal learning nor locomotion was impaired following selective deletion of Ube3a in Purkinje cells. However, genetic normalization of αCaMKII inhibitory phosphorylation fully rescued locomotor deficits despite failing to improve cerebellar learning in AS mice, suggesting extracerebellar circuit involvement in locomotor learning. We confirmed this hypothesis through cerebellum-specific reinstatement of Ube3a, which ameliorated cerebellar learning deficits but did not rescue locomotor deficits. This double dissociation of locomotion and cerebellar phenotypes strongly suggests that the locomotor deficits of AS mice do not arise from impaired cerebellar cortex function. Our results provide important insights into the etiology of the motor deficits associated with AS. PMID:26485287

Purpose: To develop and validate a semiautomatic segmentation method for thoracic cavity volumetry and mediastinum fat quantification of patients with chronic obstructive pulmonary disease. Methods: The thoracic cavity region was separated by segmenting multiorgans, namely, the rib, lung, heart, and diaphragm. To encompass various lung disease-induced variations, the inner thoracic wall and diaphragm were modeled by using a three-dimensional surface-fitting method. To improve the accuracy of the diaphragm surface model, the heart and its surrounding tissue were segmented by a two-stage level set method using a shape prior. To assess the accuracy of the proposed algorithm, the algorithm results of 50 patients were compared to the manual segmentation results of two experts with more than 5 years of experience (these manual results were confirmed by an expert thoracic radiologist). The proposed method was also compared to three state-of-the-art segmentation methods. The metrics used to evaluate segmentation accuracy were volumetric overlap ratio (VOR), false positive ratio on VOR (FPRV), false negative ratio on VOR (FNRV), average symmetric absolute surface distance (ASASD), average symmetric squared surface distance (ASSSD), and maximum symmetric surface distance (MSSD). Results: In terms of thoracic cavity volumetry, the mean ± SD VOR, FPRV, and FNRV of the proposed method were (98.17 ± 0.84)%, (0.49 ± 0.23)%, and (1.34 ± 0.83)%, respectively. The ASASD, ASSSD, and MSSD for the thoracic wall were 0.28 ± 0.12, 1.28 ± 0.53, and 23.91 ± 7.64 mm, respectively. The ASASD, ASSSD, and MSSD for the diaphragm surface were 1.73 ± 0.91, 3.92 ± 1.68, and 27.80 ± 10.63 mm, respectively. The proposed method performed significantly better than the other three methods in terms of VOR, ASASD, and ASSSD. Conclusions: The proposed semiautomatic thoracic cavity segmentation method, which extracts multiple organs (namely, the rib, thoracic wall, diaphragm, and heart

The leading symptoms of bilateral vestibulopathy (BVP) are postural imbalance and unsteadiness of gait that worsens in darkness and on uneven ground. There are typically no symptoms while sitting or lying under static conditions. A minority of patients also have movement-induced oscillopsia, in particular while walking. The diagnosis of BVP is based on a bilaterally reduced or absent function of the vestibulo-ocular reflex (VOR). This deficit is diagnosed for the high-frequency range of the angular VOR by a bilaterally pathologic bedside head impulse test (HIT) and for the low-frequency range by a bilaterally reduced or absent caloric response. If the results of the bedside HIT are unclear, angular VOR function should be quantified by a video-oculography system (vHIT). An additional test supporting the diagnosis is dynamic visual acuity. Cervical and ocular vestibular-evoked myogenic potentials (c/oVEMP) may also be reduced or absent, indicating impaired otolith function. There are different subtypes of BVP depending on the affected anatomic structure and frequency range of the VOR deficit: impaired canal function in the low- and/or high-frequency VOR range only and/or otolith function only; the latter is very rare. The etiology of BVP remains unclear in more than 50% of patients: in these cases neurodegeneration is assumed. Frequent known causes are ototoxicity mainly due to gentamicin, bilateral Menière's disease, autoimmune diseases, meningitis and bilateral vestibular schwannoma, as well as an association with cerebellar degeneration (cerebellar ataxia, neuropathy, vestibular areflexia syndrome=CANVAS). In general, in the long term there is no improvement of vestibular function. There are four treatment options: first, detailed patient counseling to explain the cause, etiology, and consequences, as well as the course of the disease; second, daily vestibular exercises and balance training; third, if possible, treatment of the underlying cause, as in bilateral

Six normal humans experienced yaw axis steps of velocity at 120 degrees /s in the dark. During the post-rotary period, subjects either had a null-task (do nothing); an ocular motor task (forced convergence: crossing the eyes); or a visual task (fixating a head-stationary target against a background of 10 degrees light/dark bars). Tasks started at 3 s post-rotation, and lasted either 2, 5, 10, or 15 s. Ocular motor and visual tasks were tested on different days. Five repetitions of each task duration were recorded for each subject. A mean VOR gain of 0.52 was observed, which did not vary with experimental conditions. Both convergence and fixation markedly suppressed nystagmus; in fact, the VORs obtained with the two different tasks are superficially similar in appearance. However, mean null-task time-constants were 9.4 s for convergence days, but 8.4 s for fixation days, and there was a small but significant reduction in overall null-task VOR amplitude on fixation days. Also, post-convergence slow-phase velocities were slightly enhanced, while post-fixation velocities were significantly reduced. The time-constant of velocity storage was found to be 10.1 s for convergence responses and 8.2 s for fixation responses. These differences can be understood in terms of modifications in central velocity storage during visual fixation which do not occur with convergence. The mean fixation data were analyzed in the context of a VOR model well-established for monkey data. With appropriate choice of parameters, this model accurately reproduces most features of the human data. An estimate for the human cupula time-constant of 3.3 s is obtained. Compared with the monkey, fixation suppression is greater and post-fixation velocity reduction less. Retinal slip alone accounts well for this; "velocity dumping" by an integrator shunt must be slight if present at all. The model correctly represents the post-fixation VOR for all durations of fixation.

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral plugging of the three semicircular canals. During the period (1-4 days) that animals were kept in darkness after plugging, the gain during steps of acceleration (3, 000 degrees /s(2), peak velocity = 150 degrees /s) was 0.61 +/- 0.14 (mean +/- SD) for contralesional rotations and 0.33 +/- 0.03 for ipsilesional rotations. Within 18-24 h after animals were returned to light, the VOR gain for contralesional rotations increased to 0. 88 +/- 0.05, whereas there was only a slight increase in the gain for ipsilesional rotations to 0.37 +/- 0.07. A symmetrical increase in the gain measured at the plateau of head velocity was noted after animals were returned to light. The latency of the VOR was 8.2 +/- 0. 4 ms for ipsilesional and 7.1 +/- 0.3 ms for contralesional rotations. The VOR evoked by sinusoidal rotations of 0.5-15 Hz, +/-20 degrees /s had no significant half-cycle asymmetries. The recovery of gain for these responses after plugging was greater at lower than at higher frequencies. Responses to rotations at higher velocities for frequencies >/=4 Hz showed an increase in contralesional half-cycle gain, whereas ipsilesional half-cycle gain was unchanged. A residual response that appeared to be canal and not otolith mediated was noted after plugging of all six semicircular canals. This response increased with frequency to reach a gain of 0.23 +/- 0.03 at 15 Hz, resembling that predicted based on a reduction of the dominant time constant of the canal to 32 ms after plugging. A model incorporating linear and nonlinear pathways was used to simulate the data. The coefficients of this model were determined from data in animals with intact vestibular function. Selective increases in the gain for the linear and nonlinear pathways predicted the changes in recovery observed after canal plugging. An increase in gain of

The gain of the vertical angular vestibuloocular reflex (aVOR) was adaptively altered by visual-vestibular mismatch during rotation about an interaural axis, using steps of velocity in three head orientations: upright, left-side down, and right-side down. Gains were decreased by rotating the animal and visual surround in the same direction and increased by visual and surround rotation in opposite directions. Gains were adapted in one head position (single-state adaptation) or decreased with one side down and increased with the other side down (dual-state adaptation). Animals were tested in darkness using sinusoidal rotation at 0.5 Hz about an interaural axis that was tilted from horizontal to vertical. They were also sinusoidally oscillated from 0.5 to 4 Hz about a spatial vertical axis in static tilt positions from yaw to pitch. After both single- and dual-state adaptation, gain changes were maximal when the monkeys were in the position in which the gain had been adapted, and the gain changes progressively declined as the head was tilted away from that position. We call this gravity-specific aVOR gain adaptation. The spatial distribution of the specific aVOR gain changes could be represented by a cosine function that was superimposed on a bias level, which we called gravity-independent gain adaptation. Maximal gravity-specific gain changes were produced by 2-4 h of adaptation for both single- and dual-state adaptations, and changes in gain were similar at all test frequencies. When adapted while upright, the magnitude and distribution of the gravity-specific adaptation was comparable to that when animals were adapted in side-down positions. Single-state adaptation also produced gain changes that were independent of head position re gravity particularly in association with gain reduction. There was no bias after dual-state adaptation. With this difference, fits to data obtained by altering the gain in separate sessions predicted the modulations in gain obtained

1. We recorded eye movements in six rhesus monkeys before and after unilateral labyrinthectomy and quantified the compensation for both the static and the dynamic disturbances of the vestibuloocular reflex (VOR). 2. When first recorded after labyrinthectomy (18-20 h postlesion), all animals had a spontaneous nystagmus with mean slow-phase velocities ranging from 24 to 54 degrees/s measured in darkness and 0-4 degrees/s measured in the light. The level of nystagmus diminished quickly, and by postoperative day 25 mean values ranged from 4 to 22 degrees/s, measured in darkness. The waveform of individual slow phases was variable, but in the first postoperative week its trajectory usually showed an increasing, or an increasing then decreasing, velocity. This finding indicates that peripheral vestibular lesions can alter the function of the ocular motor eye-position integrator. 3. The VOR gain (eye velocity/head velocity, corrected for spontaneous nystagmus) during rotations (30-300 degrees/s) in the dark was diminished from nearly 1.0 preoperatively to approximately 0.5 when first measured after labyrinthectomy, except for rotations toward the lesioned side at high speeds for which the gain was even lower. Within the first few postoperative days, for rotations toward the intact side, the VOR gain increased rapidly, to approximately 0.8. For rotations toward the lesioned side similar behavior was noted for stimuli of 30-60 degrees/s, but at higher velocities compensation proceeded more slowly. By 3 mo postoperatively gains had reached values ranging from 0.77 to 1.03 for rotations toward the intact side and from 0.61 to 0.98 for rotations toward the lesioned side. Values were higher for lower-velocity stimuli. 4. Caloric testing with ice water in the unoperated ear elicited nystagmus with a mean value of maximum slow-phase velocity of 129 degrees/s preoperatively and 195 degrees/s 3 mo postoperatively. There was no caloric response on the lesioned side. From the

Background and Purpose Tumors involving the cerebellopontine angle (CPA) pose a diagnostic challenge due to their diverse manifestations. Head impulse tests (HITs) have been used to evaluate vestibular function, but few studies have explored the head impulse gain of the vestibulo-ocular reflex (VOR) in patients with a vestibular schwannoma. This study tested whether the head impulse gain of the VOR is an indicator of the size of a unilateral CPA tumor. Methods Twenty-eight patients (21 women; age=64±12 years, mean±SD) with a unilateral CPA tumor underwent a recording of the HITs using a magnetic search coil technique. Patients were classified into non-compressing (T1-T3) and compressing (T4) groups according to the Hannover classification. Results Most (23/28, 82%) of the patients showed abnormal HITs for the semicircular canals on the lesion side. The bilateral abnormality in HITs was more common in the compressing group than the non-compressing group (80% vs. 8%, Pearson's chi-square test: p<0.001). The tumor size was inversely correlated with the head impulse gain of the VOR in either direction. Conclusions Bilaterally abnormal HITs indicate that a patient has a large unilateral CPA tumor. The abnormal HITs in the contralesional direction may be explained either by adaptation or by compression and resultant dysfunction of the cerebellar and brainstem structures. The serial evaluation of HITs may provide information on tumor growth, and thereby reduce the number of costly brain scans required when following up patients with CPA tumors. PMID:26754780

We investigated how vestibulo-spinal reflexes (VSRs) and vestibulo-ocular reflexes (VORs) measured through vestibular evoked myogenic potentials (VEMPs) and video head impulse test (vHIT) outcomes, respectively, are modulated during standing under conditions of increased postural threat. Twenty-five healthy young adults stood quietly at low (0.8 m from the ground) and high (3.2 m) surface height conditions in two experiments. For the first experiment (n = 25) VEMPs were recorded with surface EMG from inferior oblique (IO), sternocleidomastoid (SCM), trapezius (TRP), and soleus (SOL) muscles in response to 256 air-conducted short tone bursts (125 dB SPL, 500 Hz, 4 ms) delivered via headphones. A subset of subjects (n = 19) also received horizontal and vertical head thrusts (∼150°/s) at each height in a separate session, comparing eye and head velocities by using a vHIT system for calculating the functional VOR gains. VEMP amplitudes (IO, TRP, SOL) and horizontal and vertical vHIT gains all increased with high surface height conditions (P < 0.05). Changes in IO and SCM VEMP amplitudes as well as horizontal vHIT gains were correlated with changes in electrodermal activity (ρ = 0.44-0.59, P < 0.05). VEMP amplitude for the IO also positively correlated with fear (ρ = 0.43, P = 0.03). Threat-induced anxiety, fear, and arousal have significant effects on VSR and VOR gains that can be observed in both physiological and functional outcome measures. These findings provide support for a potential central modulation of the vestibular nucleus complex through excitatory inputs from neural centers involved in processing fear, anxiety, arousal, and vigilance.

There is evidence that the normal aging process is associated with impaired vestibulo-ocular reflexes (VOR) and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa’s ganglion and the vestibular nucleus complex (VNC), it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarizes and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics. PMID:26973593

We compared the ability of eight normal subjects and 15 patients with brainstem or cerebellar disease to follow a moving visual stimulus smoothly with either the eyes alone or with combined eye-head tracking. The visual stimulus was either a laser spot (horizontal and vertical planes) or a large rotating disc (torsional plane), which moved at one sinusoidal frequency for each subject. The visually enhanced Vestibulo-Ocular Reflex (VOR) was also measured in each plane. In the horizontal and vertical planes, we found that if tracking gain (gaze velocity/target velocity) for smooth pursuit was close to 1, the gain of combined eye-hand tracking was similar. If the tracking gain during smooth pursuit was less than about 0.7, combined eye-head tracking was usually superior. Most patients, irrespective of diagnosis, showed combined eye-head tracking that was superior to smooth pursuit; only two patients showed the converse. In the torsional plane, in which optokinetic responses were weak, combined eye-head tracking was much superior, and this was the case in both subjects and patients. We found that a linear model, in which an internal ocular tracking signal cancelled the VOR, could account for our findings in most normal subjects in the horizontal and vertical planes, but not in the torsional plane. The model failed to account for tracking behaviour in most patients in any plane, and suggested that the brain may use additional mechanisms to reduce the internal gain of the VOR during combined eye-head tracking. Our results confirm that certain patients who show impairment of smooth-pursuit eye movements preserve their ability to smoothly track a moving target with combined eye-head tracking.

We investigated the pathogenesis of acquired pendular nystagmus (APN) in six patients, three of whom had multiple sclerosis. First, we tested the hypothesis that the oscillations of APN are due to a delay in visual feedback secondary, for example, to demyelination of the optic nerves. We manipulated the latency to onset of visually guided eye movements using an electronic technique that induces sinusoidal oscillations in normal subjects. This manipulation did not change the characteristics of the APN, but did superimpose lower-frequency oscillations similar to those induced in normal subjects. These results are consistent with current models for smooth (non-saccadic) eye movements, which predict that prolongation of visual feedback could not account for the high-frequency oscillations that often characterize APN. Secondly, we attempted to determine whether an increase in the gain of the visually-enhanced vestibulo-ocular reflex (VOR), produced by viewing a near target, was accompanied by a commensurate increase in the amplitude of APN. Increases in horizontal or vertical VOR gain during near viewing occurred in four patients, but only two of them showed a parallel increase in APN amplitude. On the other hand, APN amplitude decreased during viewing of the near target in the two patients who showed no change in VOR gain. Taken together, these data suggest that neither delayed visual feedback nor a disorder of central vestibular mechanisms is primarily responsible for APN. More likely, these ocular oscillations are produced by abnormalities of internal feedback circuits, such as the reciprocal connections between brainstem nuclei and cerebellum.

This article reviews vestibular pathology and the requirements and progress made in the design and construction of a vestibular prosthesis. Bilateral loss of vestibular sensation is disabling. When vestibular hair cells are injured by ototoxic medications or other insults to the labyrinth, the resulting loss of sensory input disrupts vestibulo-ocular reflexes (VORs) and vestibulo-spinal reflexes that normally stabilize the eyes and body. Affected individuals suffer poor vision during head movement, postural instability, chronic disequilibrium, and cognitive distraction. Although most individuals with residual sensation compensate for their loss over time, others fail to do so and have no adequate treatment options. A vestibular prosthesis analogous to cochlear implants but designed to modulate vestibular nerve activity during head movement should improve quality of life for these chronically dizzy individuals. We describe the impact of bilateral loss of vestibular sensation, animal studies supporting feasibility of prosthetic vestibular stimulation, the current status of multichannel vestibular sensory replacement prosthesis development, and challenges to successfully realizing this approach in clinical practice. In bilaterally vestibular-deficient rodents and rhesus monkeys, the Johns Hopkins multichannel vestibular prosthesis (MVP) partially restores the three-dimensional (3D) VOR for head rotations about any axis. Attempts at prosthetic vestibular stimulation of humans have not yet included the 3D eye movement assays necessary to accurately evaluate VOR alignment, but these initial forays have revealed responses that are otherwise comparable to observations in animals. Current efforts now focus on refining electrode design and surgical technique to enhance stimulus selectivity and preserve cochlear function, optimizing stimulus protocols to improve dynamic range and reduce excitation–inhibition asymmetry, and adapting laboratory MVP prototypes into devices

Coordinated movements between the eyes and head are required to maintain a stable retinal image during head and body motion. The vestibulo-ocular reflex (VOR) plays a significant role in this gaze control system that functions well for most daily activities. However, certain environmental conditions or interruptions in normal VOR function can lead to inadequate ocular compensation, resulting in oscillopsia, or blurred vision. It is therefore possible to use acuity to determine when the environmental conditions, VOR function, or the combination of the two is not conductive for maintaining clear vision. Over several years we have designed and tested several tests of dynamic visual acuity (DVA). Early tests used the difference between standing and walking acuity to assess decrements in the gaze stabilization system after spaceflight. Supporting ground-based studies measured the responses from patients with bilateral vestibular dysfunction and explored the effects of visual target viewing distance and gait cycle events on walking acuity. Results from these studies show that DVA is affected by spaceflight, is degraded in patients with vestibular dysfunction, changes with target distance, and is not consistent across the gait cycle. We have recently expanded our research to include studies in which seated subjects are translated or rotated passively. Preliminary results from this work indicate that gaze stabilization ability may differ between similar active and passive conditions, may change with age, and can be affected by the location of the visual target with respect to the axis of motion. Use of DVA as a diagnostic tool is becoming more popular but the functional nature of the acuity outcome measure also makes it ideal for identifying conditions that could lead to degraded vision. By doing so, steps can be taken to alter the problematic environments to improve the man-machine interface and optimize performance.

The flocculus and ventral paraflocculus are adjacent regions of the cerebellar cortex that are essential for controlling smooth pursuit eye movements and for altering the performance of the vestibulo-ocular reflex (VOR). The question addressed in this study is whether these regions of the cerebellum are more globally involved in controlling gaze, regardless of whether eye or active head movements are used to pursue moving visual targets. Single-unit recordings were obtained from Purkinje (Pk) cells in the floccular region of squirrel monkeys that were trained to fixate and pursue small visual targets. Cell firing rate was recorded during smooth pursuit eye movements, cancellation of the VOR, combined eye-head pursuit, and spontaneous gaze shifts in the absence of targets. Pk cells were found to be much less sensitive to gaze velocity during combined eye-head pursuit than during ocular pursuit. They were not sensitive to gaze or head velocity during gaze saccades. Temporary inactivation of the floccular region by muscimol injection compromised ocular pursuit but had little effect on the ability of monkeys to pursue visual targets with head movements or to cancel the VOR during active head movements. Thus the signals produced by Pk cells in the floccular region are necessary for controlling smooth pursuit eye movements but not for coordinating gaze during active head movements. The results imply that individual functional modules in the cerebellar cortex are less involved in the global organization and coordination of movements than with parametric control of movements produced by a specific part of the body.

Video head impulse test (vHIT) is a new testing which able to identify the overt and covert saccades and study the gain of vestibulo-ocular reflex (VOR) of each semicircular canal. The aim of this study is to review the clinical use of vHIT in patients with vestibular disorders in different diseases. PubMed and Cochrane databases were searched for all articles that defined vHIT, compared vHIT with another clinical test, and studied the efficacy of vHIT as diagnostic tools with vestibular disease. 37 articles about vHIT were reviewed. All articles studied the vHIT in English and French languages up to May 2015 were included in the review. Editorial articles or short comments, conference abstracts, animal studies, and language restriction were excluded from the review. Four systems were used in the literature to do the vHIT. vHIT is physiological quick test, which studied the VOR at high frequency of each semicircular canal by calculating the duration ratio between the head impulse and gaze deviation. vHIT is more sensitive than clinical head impulse test (cHIT), especially in patient with isolated covert saccades. vHIT test is diagnostic of vestibular weakness by gain reduction and the appearance of overt and covert saccades. If the vHIT is normal, then caloric test is mandatory to rule out a peripheral origin of vertigo. It is recommended to test each semicircular canal, as isolated vertical canal weakness was identified in the literature. More investigation would be required to determine the evolution of the VOR gain with the progression of the vestibular disease.

Short-radius centrifugation is a potential countermeasure against the effects of prolonged weightlessness. Head movements in a rotating environment, however, induce serious side effects: inappropriate vestibular ocular reflexes (VOR), body-tilt illusions and motion sickness induced by cross-coupled accelerations on a rotating platform. These are well predicted by a semicircular canal model. The present study investigates cognitive effects on the inappropriate VOR and the illusory sensations experienced by subjects rotating on a short-radius centrifuge (SRC). Subjects (N=19) were placed supine on a rotating horizontal bed with their head at the center of rotation. To investigate the extent to which they could control their sensations voluntarily, subjects were asked alternatively to "fight" (i.e. to try to resist and suppress) those sensations, or to "go" with (i.e. try to enhance or, at least, acquiesce in) them. The only significant effect on the VOR of this cognitive intervention was to diminish the time constant characterizing the decay of the nystagmus in subjects who had performed the "go" (rather than the "fight") trials. However, illusory sensations, as measured by reported subjective intensities, were significantly less intense during the "fight" than during the "go" trials. These measurements also verified an asymmetry in illusory sensation known from earlier experiments: the illusory sensations are greater when the head is rotated from right ear down (RED) to nose up (NU) posture than from NU to RED. The subjects habituated, modestly, to the rotation between their first and second sequences of trials, but showed no better (or worse) suppression of illusory sensations thereafter. No significant difference in habituation was observed between the "fight" and "go" trials.

Both yaw and pitch visual-vestibular interactions at two separate frequencies of chair rotation (0.2 and 0.8 Hz) in combination with a single velocity of optokinetic stimulus (36 degrees/s) were used to investigate the effects of sustained weightlessness on neural strategies adopted by astronaut subjects to cope with the stimulus rearrangement of spaceflight. Pitch and yaw oscillation in darkness at 0.2 and 0.8 Hz without optokinetic stimulation, and constant velocity linear optokinetic stimulation at 18, 36, and 54 degrees/s presented relative to the head with the subject stationary, were used as controls for the visual-vestibular interactions. The results following 8 days of space flight showed no significant changes in: (1) either the horizontal and vertical vestibulo-ocular reflex (VOR) gain, phase, or bias; (2) the yaw visual-vestibular response (VVR); or (3) the horizontal or vertical optokinetic (OKN) slow phase velocity (SPV). However, significant changes were observed: (1) when during pitch VVR at 0.2 Hz late inflight, the contribution of the optokinetic input to the combined oculomotor response was smaller than during the stationary OKN SPV measurements, followed by an increased contribution during the immediate postflight testing; and (2) when during pitch VVR at 0.8 Hz, the component of the combined oculomotor response due to the underlying vertical VOR was more efficiently suppressed early inflight and less suppressed immediately postflight compared with preflight observations. The larger OKN response during pitch VVR at 0.2 Hz and the better suppression of VOR during pitch VVR at 0.8 Hz postflight are presumably due to the increased role of vision early inflight and immediately after spaceflight, as previously observed in various studies. These results suggest that the subjects adopted a neural strategy to structure their spatial orientation in weightlessness by reweighting visual, otolith, and perhaps tactile/somatic signals.

Head movements in the sagittal pitch plane typically involve off-axis rotation requiring both vertical and horizontal vergence ocular reflexes to compensate for angular and translational motion relative to visual targets of interest. The purpose of this study was to compare passive pitch VOR responses during rotation about an Earth-vertical axis (canal only cues) with off-axis rotation (canal and otolith cues). Methods. Eleven human subjects were oscillated sinusoidally at 0.13, 0.3 and 0.56 Hz while lying left-side down with the interaural axis either aligned with the axis of rotation or offset by 50 cm. In a second set of measurements, twelve subjects were also tested during sinusoidally varying centrifugation over the same frequency range. The modulation of vertical and horizontal vergence ocular responses was measured with a binocular videography system. Results. Off-axis pitch rotation enhanced the vertical VOR at lower frequencies and enhanced the vergence VOR at higher frequencies. During sinusoidally varying centrifugation, the opposite trend was observed for vergence, with both vertical and vergence vestibulo-ocular reflexes being suppressed at the highest frequency. Discussion. These differential effects of off-axis rotation over the 0.13 to 0.56 Hz range are consistent with the hypothesis that otolith-ocular reflexes are segregated in part on the basis of stimulus frequency. At the lower frequencies, tilt otolith-ocular responses compensate for declining canal input. At higher frequencies, translational otolith-ocular reflexes compensate for declining visual contributions to the kinematic demands required for fixating near targets.

Dizziness and imbalance are clinically poorly defined terms, which affect ~30% of people over 65 years of age. In these people, it is often difficult to define the primary cause of dizziness, as it can stem from cardiovascular, vestibular, psychological, and neuromuscular causes. However, identification of the primary cause is vital in determining the most effective treatment strategy for a patient. Our aim is to accurately identify the prevalence of benign paroxysmal positional vertigo (BPPV), peripheral, and central vestibular hypofunction in people aged over 50 years who had experienced dizziness within the past year. Seventy-six participants aged 51–92 (mean ± SD = 69 ± 9.5 years) were tested using the head thrust dynamic visual acuity (htDVA) test, dizziness handicap inventory (DHI), as well as sinusoidal and unidirectional rotational chair testing, in order to obtain data for htDVA score, DHI score, sinusoidal (whole-body, 0.1–2 Hz with peak velocity at 30°/s) vestibulo-ocular reflex (VOR) gain and phase, transient (whole-body, acceleration at 150°/s2 to a constant velocity rotation of 50°/s) VOR gain and time constant (TC), optokinetic nystagmus (OKN) gain, and TC (whole-body, constant velocity rotation at 50°/s). We found that BPPV, peripheral and central vestibular hypofunction were present in 38 and 1% of participants, respectively, suggesting a likely vestibular cause of dizziness in these people. Of those with a likely vestibular cause, 63% had BPPV; a figure higher than previously reported in dizziness clinics of ~25%. Our results indicate that htDVA, sinusoidal (particularly 0.5–1 Hz), and transient VOR testing were the most effective at detecting people with BPPV or vestibular hypofunction, whereas DHI and OKN were effective at only detecting non-BPPV vestibular hypofunction. PMID:26733940

The vestibulo-ocular reflex (VOR) generates eye rotation to compensate for potential retinal slip in the specific plane of head movement. Dynamic visual acuity (DVA) has been utilized as a functional measure of the VOR. The purpose of this study was to examine changes in accuracy and reaction time when performing a DVA task with targets offset from the plane of rotation, e.g. offset vertically during horizontal rotation. Visual acuity was measured in 12 healthy subjects as they moved a hand-held joystick to indicate the orientation of a computer-generated Landolt C "as quickly and accurately as possible." Acuity thresholds were established with optotypes presented centrally on a wall-mounted LCD screen at 1.3 m distance, first without motion (static condition) and then while oscillating at 0.8 Hz (DVA, peak velocity 60 deg/s). The effect of target location was then measured during horizontal rotation with the optotypes randomly presented in one of nine different locations on the screen (offset up to 10 deg). The optotype size (logMar 0, 0.2 or 0.4, corresponding to Snellen range 20/20 to 20/50) and presentation duration (150, 300 and 450 ms) were counter-balanced across five trials, each utilizing horizontal rotation at 0.8 Hz. Dynamic acuity was reduced relative to static acuity in 7 of 12 subjects by one step size. During the random target trials, both accuracy and reaction time improved proportional to optotype size. Accuracy and reaction time also improved between 150 ms and 300 ms presentation durations. The main finding was that both accuracy and reaction time varied as a function of target location, with greater performance decrements when acquiring vertical targets. We conclude that dynamic visual acuity varies with target location, with acuity optimized for targets in the plane of motion. Both reaction time and accuracy are functionally relevant DVA parameters of VOR function.

Background: Emergence of resistance to respective antifungal drugs is a primary concern for the treatment of candidiasis. Hence, determining antifungal susceptibility of the isolated yeasts is of special importance for effective therapy. For this purpose, the clinical laboratory standard institute (CLSI) has introduced a broth microdilution method to determine minimum inhibitory concentration (MIC). However, the so-called “Trailing effect” phenomenon might sometimes pose ambiguity in the interpretation of the results. Objectives: The present study aimed to determine the in vitro susceptibility of clinical isolates of Candida against azoles and the frequency of the Trailing effect. Materials and Methods: A total of 193 Candida isolates were prospectively collected and identified through the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Using a broth microdilution test, according to the guidelines of CLSI M27-A3, antifungal susceptibilities of the isolated yeasts against Fluconazole (FLU), Itraconazole (ITR), Ketoconazole (KET) and Voriconazole (VOR) were assessed. Moreover, trailing growth was determined when a susceptible MIC was incubated for 24 hours, and turned into a resistant one after 48 hours of incubation. Results: Among the tested antifungal drugs in this study, the highest rate of resistance was observed against ITR (28.5%) followed by VOR (26.4%), FLU (20.8%) and KET (1.5%). The trailing effect was induced in 27 isolates (14.0%) by VOR, in 26 isolates (13.5%) by ITR, in 24 isolates (12.4%) by FLU, and in 19 isolates (9.8%) by KET. Conclusions: The monitoring of antifungal susceptibilities of Candida species isolated from clinical sources is highly recommended for the efficient management of patients. Moreover, the trailing effect should be taken into consideration once the interpretation of the results is intended. PMID:27127587

We recorded the horizontal (yaw), vertical (pitch), and torsional (roll) eye movements of two rhesus monkeys with scleral search coils before and after the COSMOS Biosatellite 2229 Flight. The aim was to determine effects of adaptation to microgravity on the vestibulo-ocular reflex (VOR). The animals flew for 11 days. The first postflight tests were 22 h and 55 h after landing, and testing extended for 11 days after reentry. There were four significant effects of spaceflight on functions related to spatial orientation: (1) Compensatory ocular counterrolling (OCR) was reduced by about 70% for static and dynamic head tilts with regard to gravity. The reduction in OCR persisted in the two animals throughout postflight testing. (2) The gain of the torsional component of the angular VOR (roll VOR) was decreased by 15% and 50% in the two animals over the same period. (3) An up-down asymmetry of nystagmus, present in the two monkeys before flight was reduced after exposure to microgravity. (4) The spatial orientation of velocity storage was shifted in the one monkey that could be tested soon after flight. Before flight, the yaw axis eigenvector of optokinetic afternystagmus was close to gravity when the animal was upright or tilted. After flight, the yaw orientation vector was shifted toward the body yaw axis. By 7 days after recovery, it had reverted to a gravitational orientation. We postulate that spaceflight causes changes in the vestibular system which reflect adaptation of spatial orientation from a gravitational to a body frame of reference. These changes are likely to play a role in the postural, locomotor, and gaze instability demonstrated on reentry after spaceflight.

The objective is to determine the relationship of motion sickness susceptibility to vestibulo-ocular reflexes (VOR), motion perception, and behavioral utilization of sensory orientation cues for the control of postural equilibrium. The work is focused on reflexes and motion perception associated with pitch and roll movements that stimulate the vertical semicircular canals and otolith organs of the inner ear. This work is relevant to the space motion sickness problem since 0 g related sensory conflicts between vertical canal and otolith motion cues are a likely cause of space motion sickness.

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This paper briefly reviews tentative requirements for global, earth-referenced sole means of navigation systems with emphasis on integrity and availability. These requirements can be allocated to integrated navigation system architectures based on for instance GPS, GLONASS, VOR/DME, TACAN, Omega, Chayka, and Loran-C. Fault detection and isolation techniques (FDI) for integrated radio navigation systems are presented. The FDI algorithm provides a protection radius with a specified confidence level as a function of measurement geometry and algorithm requirements. This is followed by a case study of integrated GPS/Loran-C.

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Spatial transformations of the vestibular-optokinetic system must account for changes in head position with respect to gravity in order to produce compensatory oculomotor responses. The purpose of this experiment was to study the influence of gravity on the vestibulo-ocular reflex (VOR) in darkness and on visual-vestibular interaction in the pitch plane in human subjects using two different comparisons: (1) Earth-horizontal axis (EHA) rotation about an upright versus a supine body orientation, and (2) Earth-horizontal versus Earth-vertical (EVA) rotation axes. Visual-vestibular responses (VVR) were evaluated by measuring the slow phase velocity of nystagmus induced during sinusoidal motion of the body in the pitch plane (at 0.2 Hz and 0.8 Hz) combined with a constant-velocity vertical optokinetic stimulation (at +/- 36 degrees/s). The results showed no significant effect on the gain or phase of the VOR in darkness or on the VVR responses at 0.8 Hz between EHA upright and EHA supine body orientations. However, there was a downward shift in the VOR bias in darkness in the supine orientation. There were systematic changes in VOR and VVR between EHA and EVA for 0.2 Hz, including a reduced modulation gain, increased phase lead, and decreased bias during EVA rotation. The same trend was also observed at 0.8 Hz, but at a lesser extent, presumably due to the effects of eccentric rotation in our EVA condition and/or to the different canal input across frequencies. The change in the bias at 0.2 Hz between rotation in darkness and rotation with an optokinetic stimulus was greater than the optokinetic responses without rotation. During EHA, changes in head position relative to gravity preserve graviceptor input to the VVR regardless of body orientation. However, the modifications in VVR gain and phase when the rotation axis is aligned with gravity indicate that this graviceptive information is important for providing compensatory eye movements during visual

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Patients with bilateral vestibular failure (BVF) suffer from gait unsteadiness, oscillopsia and impaired spatial orientation. Brain imaging studies applying caloric irrigation to patients with BVF have shown altered neural activity of cortical visual–vestibular interaction: decreased bilateral neural activity in the posterior insula and parietal operculum and decreased deactivations in the visual cortex. It is unknown how this affects functional connectivity in the resting brain and how changes in connectivity are related to vestibular impairment. We applied a novel data driven approach based on graph theory to investigate altered whole-brain resting-state functional connectivity in BVF patients (n= 22) compared to age- and gender-matched healthy controls (n= 25) using resting-state fMRI. Changes in functional connectivity were related to subjective (vestibular scores) and objective functional parameters of vestibular impairment, specifically, the adaptive changes during active (self-guided) and passive (investigator driven) head impulse test (HIT) which reflects the integrity of the vestibulo-ocular reflex (VOR). BVF patients showed lower bilateral connectivity in the posterior insula and parietal operculum but higher connectivity in the posterior cerebellum compared to controls. Seed-based analysis revealed stronger connectivity from the right posterior insula to the precuneus, anterior insula, anterior cingulate cortex and the middle frontal gyrus. Excitingly, functional connectivity in the supramarginal gyrus (SMG) of the inferior parietal lobe and posterior cerebellum correlated with the increase of VOR gain during active as compared to passive HIT, i.e., the larger the adaptive VOR changes the larger was the increase in regional functional connectivity. Using whole brain resting-state connectivity analysis in BVF patients we show that enduring bilateral deficient or missing vestibular input leads to changes in resting-state connectivity of the brain

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A flight evaluation of LORAN C as a supplement to existing navigation aids for general aviation aircraft, particularly in mountainous regions of the United States and where VOR coverage is limited was conducted. Flights, initiated in the summer months, extend through four seasons and practically all weather conditions typical of northeastern U.S. operations. Assessment of all the data available indicates that LORAN C signals are suitable as a means of navigation during enroute, terminal and nonprecision approach operations and the performance exceeds the minimum accuracy criteria.

vestibular stimulation. Eye movements induced by EVAR showed an increased phase lead during reaction-time tasks, suggesting altered vestibulo-ocular reflex (VOR) dynamics, possibly based on cerebellar-mediated changes in velocity storage. Since fixation of a head-fixed visual target did not add to the effect of rotation in the dark, a further implication of our results is that VOR-fixation while performing a concurrent information-processing task may be accomplished primarily by VOR suppression rather than by VOR cancellation.

Spatial transformations of the vestibular-optokinetic system must account for changes in head position with respect to gravity in order to produce compensatory oculomotor responses. The purpose of this experiment was to study the influence of gravity on the vestibulo-ocular reflex (VOR) in darkness and on visual-vestibular interaction in the pitch plane in human subjects using two different comparisons: (1) Earth-horizontal axis (EHA) rotation about an upright versus a supine body orientation, and (2) Earth-horizontal versus Earth-vertical (EVA) rotation axes. Visual-vestibular responses (VVR) were evaluated by measuring the slow phase velocity of nystagmus induced during sinusoidal motion of the body in the pitch plane (at 0.2 Hz and 0.8 Hz) combined with a constant-velocity vertical optokinetic stimulation (at +/- 36 degrees/s). The results showed no significant effect on the gain or phase of the VOR in darkness or on the VVR responses at 0.8 Hz between EHA upright and EHA supine body orientations. However, there was a downward shift in the VOR bias in darkness in the supine orientation. There were systematic changes in VOR and VVR between EHA and EVA for 0.2 Hz, including a reduced modulation gain, increased phase lead, and decreased bias during EVA rotation. The same trend was also observed at 0.8 Hz, but at a lesser extent, presumably due to the effects of eccentric rotation in our EVA condition and/or to the different canal input across frequencies. The change in the bias at 0.2 Hz between rotation in darkness and rotation with an optokinetic stimulus was greater than the optokinetic responses without rotation. During EHA, changes in head position relative to gravity preserve graviceptor input to the VVR regardless of body orientation. However, the modifications in VVR gain and phase when the rotation axis is aligned with gravity indicate that this graviceptive information is important for providing compensatory eye movements during visual

1. Yaw eye in head (Eh) and head on body velocities (Hb) were measured in two monkeys that ran around the perimeter of a circular platform in darkness. The platform was stationary or could be counterrotated to reduce body velocity in space (Bs) while increasing gait velocity on the platform (Bp). The animals were also rotated while seated in a primate chair at eccentric locations to provide linear and angular accelerations similar to those experienced while running. 2. Both animals had head and eye nystagmus while running in darkness during which slow phase gaze velocity on the body (Gb) partially compensated for body velocity in space (Bs). The eyes, driven by the vestibuloocular reflex (VOR), supplied high-frequency characteristics, bringing Gb up to compensatory levels at the beginning and end of the slow phases. The head provided substantial gaze compensation during the slow phases, probably through the vestibulocollic reflex (VCR). Synchronous eye and head quick phases moved gaze in the direction of running. Head movements occurred consistently only when animals were running. This indicates that active body and limb motion may be essential for inducing the head-eye gaze synergy. 3. Gaze compensation was good when running in both directions in one animal and in one direction in the other animal. The animals had long VOR time constants in these directions. The VOR time constant was short to one side in one animal, and it had poor gaze compensation in this direction. Postlocomotory nystagmus was weaker after running in directions with a long VOR time constant than when the animals were passively rotated in darkness. We infer that velocity storage in the vestibular system had been activated to produce continuous Eh and Hb during running and to counteract postrotatory afterresponses. 4. Continuous compensatory gaze nystagmus was not produced by passive eccentric rotation with the head stabilized or free. This indicates that an aspect of active locomotion, most

Subjects seated in a vertical axis rotation chair controlled their rotational velocity by adjusting a potentiometer. Their goal was to null out pseudorandom rotational perturbations in order to remain perceptually stationary. Most subjects showed a slow linear drift of velocity (a constant acceleration) to one side when they were deprived of an earth-fixed visual reference. The amplitude and direction of this drift can be considered a measure of a static bias in the subject's perception of rotation. The presence of a perceptual bias is consistent with a small, constant imbalance of vestibular function which could be of either central or peripheral origin. Deviations from perfect vestibulo-ocular reflex (VOR) symmetry are also assumed to be related to imbalances in either peripheral or central vestibular function. Researchers looked for correlations between perceptual bias and various measures of vestibular reflex symmetry that might suggest a common source for both reflective and perceptual imbalances. No correlations were found. Measurement errors could not account for these results since repeated tests on the same subjects of both perceptual bias and VOR symmetry were well correlated.

We investigated the perception of self-rotation using constant-velocity chair rotations. Subjects signalled self motion during three independent tasks (1) by pushing a button when rotation was first sensed, when velocity reached a peak, when velocity began to decrease, and when velocity reached zero, (2) by rotating a disc to match the perceived motion of the body, or (3) by changing the static position of the dial such that a bigger change in its position correlated with a larger perceived velocity. All three tasks gave a consistent quantitative measure of perceived angular velocity. We found a delay in the time at which peak velocity of self-rotation was perceived (2-5 s) relative to the beginning or to the end of chair rotation. In addition the decay of the perception of self-rotation was preceded by a sensed constant-velocity interval or plateau (9-14 s). This delay in the rise of self-motion perception, and the plateau for the maximum perceived velocity, contrasts with the rapid rise and the immediate decay of the angular vestibuloocular reflex (aVOR). This difference suggests that the sensory signal from the semicircular canals undergoes additional neural processing, beyond the contribution of the velocity-storage mechanism of the aVOR, to compute the percept of self-motion.

The sensory hair cells of the inner ear undergo apoptosis after acoustic trauma or aminoglycoside antibiotic treatment, causing permanent auditory and vestibular deficits in humans. Previous studies have demonstrated a role for caspase activation in hair cell death and ototoxic injury that can be reduced by concurrent treatment with caspase inhibitors in vitro. In this study, we examined the protective effects of caspase inhibition on hair cell death in vivo after systemic injections of aminoglycosides. In one series of experiments, chickens were implanted with osmotic pumps that administrated the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (zVAD) into inner ear fluids. One day after the surgery, the animals received a 5 d course of treatment with streptomycin, a vestibulotoxic aminoglycoside. Direct infusion of zVAD into the vestibule significantly increased hair cell survival after streptomycin treatment. A second series of experiments determined whether rescued hair cells could function as sensory receptors. Animals treated with streptomycin displayed vestibular system impairment as measured by a greatly reduced vestibulo-ocular response (VOR). In contrast, animals that received concurrent systemic administration of zVAD with streptomycin had both significantly greater hair cell survival and significantly increased VOR responses, as compared with animals treated with streptomycin alone. These findings suggest that inhibiting the activation of caspases promotes the survival of hair cells and protects against vestibular function deficits after aminoglycoside treatment.

Background. False negative fistula testing in patients with chronic suppurative otitis media is a dilemma when proceeding to surgery. It is imperative to rule out a dead labyrinth or a mass effect secondary to the cholesteatoma in an otherwise normally functioning inner ear. We present a case series of three patients in whom a bedside vestibuloocular reflex (VOR) evaluation using a head impulse test was used successfully for further evaluation prior to surgery. Results. In all three cases with a false negative fistula test we were able to further evaluate at the bedside and were not only able to register the abnormal VOR but also localize its deterioration to a particular semicircular canal eroded by the fistula. Conclusion. Vestibuloocular reflex evaluation is mandatory in patients with suspected labyrinthine fistula due to cholesteatoma of the middle ear before proceeding to surgery. We demonstrate successful use of a bedside head impulse test for further evaluation prior to surgery in patients with false negative fistula test. PMID:28386500

We have developed a new technique for analyzing the rotation vector of eye movement in three dimensions with an infrared CCD camera based on the following four assumptions; i) the eye rotates on a point; ii) the pupil edge is a circle; iii) the distance from the center of eye rotation to pupil circle remains unchanged despite the rotation; iv) the image of the eye by the CCD camera is projected onto a plane which is perpendicular to the camera axis. After taking digital images of voluntary circular eye movements, we first constructed a three-dimensional frame of reference fixed on the orbita of the subject wearing a goggle equipped with an infrared CCD camera, and determined the space coordinates of the center of eye rotation, the center of the pupil, and an iris freckle. We then took digital images of the eye movements during a saccade or vestibulo-ocular reflex (VOR) and analyzed the axis and angle of the eye movements by the trajectories of the center of the pupil and the iris freckle. Finally, Listing's plane of saccade and the gain and the phase of VOR were obtained. The suitability of this technique is examined.

Next Generation Life Support (NGLS) is one of over twenty technology development projects sponsored by NASA's Game Changing Development Program. The NGLS Project develops selected life support technologies needed for humans to live and work productively in space, with focus on technologies for future use in spacecraft cabin and space suit applications. Over the last three years, NGLS had five main project elements: Variable Oxygen Regulator (VOR), Rapid Cycle Amine (RCA) swing bed, High Performance (HP) Extravehicular Activity (EVA) Glove, Alternative Water Processor (AWP) and Series-Bosch Carbon Dioxide Reduction. The RCA swing bed, VOR and HP EVA Glove tasks are directed at key technology needs for the Portable Life Support System (PLSS) and pressure garment for an Advanced Extravehicular Mobility Unit (EMU). Focus is on prototyping and integrated testing in cooperation with the Advanced Exploration Systems (AES) Advanced EVA Project. The HP EVA Glove Element, new this fiscal year, includes the generation of requirements and standards to guide development and evaluation of new glove designs. The AWP and Bosch efforts focus on regenerative technologies to further close spacecraft cabin atmosphere revitalization and water recovery loops and to meet technology maturation milestones defined in NASA's Space Technology Roadmaps. These activities are aimed at increasing affordability, reliability, and vehicle self-sufficiency while decreasing mass and mission cost, supporting a capability-driven architecture for extending human presence beyond low-Earth orbit, along a human path toward Mars. This paper provides a status of current technology development activities with a brief overview of future plans.

In an effort to clear persistent HIV infection and achieve a durable therapy-free remission of HIV disease, extensive pre-clinical studies and early pilot clinical trials are underway to develop and test agents that can reverse latent HIV infection and present viral antigen to the immune system for clearance. It is, therefore, critical to understand the impact of latency-reversing agents (LRAs) on the function of immune effectors needed to clear infected cells. We assessed the impact of LRAs on the function of natural killer (NK) cells, the main effector cells of the innate immune system. We studied the effects of three histone deacetylase inhibitors [SAHA or vorinostat (VOR), romidepsin, and panobinostat (PNB)] and two protein kinase C agonists [prostratin (PROST) and ingenol] on the antiviral activity, cytotoxicity, cytokine secretion, phenotype, and viability of primary NK cells. We found that ex vivo exposure to VOR had minimal impact on all parameters assessed, while PNB caused a decrease in NK cell viability, antiviral activity, and cytotoxicity. PROST caused non-specific NK cell activation and, interestingly, improved antiviral activity. Overall, we found that LRAs can alter the function and fate of NK cells, and these effects must be carefully considered as strategies are developed to clear persistent HIV infection. PMID:27708642

Vestibular reflexes act to stabilize the head and eyes in space during locomotion. Head stability is essential for postural control, whereas retinal image stability enhances visual acuity and may be essential for an animal to distinguish self-motion from that of an object in the environment. Guinea pig eye and head movements were measured during passive whole-body rotation in order to assess the efficacy of vestibular reflexes. The vestibulo-ocular reflex (VOR) produced compensatory eye movements with a latency of approximately 7 ms that compensated for 46% of head movement in the dark and only slightly more in the light (54%). Head movements, in response to abrupt body rotations, also contributed to retinal stability (21% in the dark; 25% in the light) but exhibited significant variability. Although compensatory eye velocity produced by the VOR was well correlated with head-in-space velocity, compensatory head-on-body speed and direction were variable and poorly correlated with body speed. The compensatory head movements appeared to be determined by passive biomechanical (e.g., inertial effects, initial tonus) and active mechanisms (the vestibulo-collic reflex or VCR). Chemically induced, bilateral lesions of the peripheral vestibular system abolished both compensatory head and eye movement responses.